Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke

Juliane Schweizer; Markus Arnold; Inke R König; Antonela Bicvic; Laura P Westphal; Valerie Schütz; Corinne Inauen; Natalie Scherrer; Andreas Luft; Marian Galovic; Carolina Ferreira Atuesta; Thomas Pokorny; Marcel Arnold; Urs Fischer; Leo H Bonati; Gian Marco De Marchis; Timo Kahles; Krassen Nedeltchev; Carlo W Cereda; Georg Kägi; Alejandro Bustamante; Joan Montaner; Georg Ntaios; Dimitrios Sagris; Christian Foerch; Katharina Spanaus; Arnold von Eckardstein; Mira Katan

doi:10.1016/j.jacc.2022.01.042

Measurement of Midregional Pro-Atrial Natriuretic Peptide to Discover Atrial Fibrillation in Patients With Ischemic Stroke

J Am Coll Cardiol. 2022 Apr 12;79(14):1369-1381. doi: 10.1016/j.jacc.2022.01.042.

Authors

Juliane Schweizer¹, Markus Arnold², Inke R König³, Antonela Bicvic⁴, Laura P Westphal¹, Valerie Schütz¹, Corinne Inauen¹, Natalie Scherrer¹, Andreas Luft¹, Marian Galovic¹, Carolina Ferreira Atuesta⁵, Thomas Pokorny¹, Marcel Arnold⁶, Urs Fischer⁶, Leo H Bonati⁷, Gian Marco De Marchis⁷, Timo Kahles⁸, Krassen Nedeltchev⁸, Carlo W Cereda⁹, Georg Kägi¹⁰, Alejandro Bustamante¹¹, Joan Montaner¹², Georg Ntaios¹³, Dimitrios Sagris¹³, Christian Foerch¹⁴, Katharina Spanaus¹⁵, Arnold von Eckardstein¹⁵, Mira Katan¹

Affiliations

¹ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
² Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: [email protected].
³ Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, University of Lübeck, Kiel, Germany.
⁴ Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland; Department of Neurology, University Hospital Bern, Bern, Switzerland.
⁵ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Department of Neurology, University Hospital Bern, Bern, Switzerland.
⁷ Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁸ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
⁹ Stroke Center Ente Ospedaliero Cantonale, Neurocenter of Southern Switzerland, Regional Hospital of Lugano, Lugano, Switzerland.
¹⁰ Department of Neurology, University Hospital Bern, Bern, Switzerland; Department of Neurology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
¹¹ Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Barcelona, Spain.
¹² Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Barcelona, Spain; Stroke Research Program, Instituto de Biomedicina de Sevilla/Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/University of Seville, Seville, Spain; Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain.
¹³ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
¹⁴ Department of Neurology, Goethe University, Frankfurt am Main, Germany.
¹⁵ Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland.

PMID: 35393018
DOI: 10.1016/j.jacc.2022.01.042

Abstract

Background: Midregional pro-atrial natriuretic peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS).

Objectives: This study aimed to determine the role of MR-proANP for classification as cardioembolic (CE) stroke, identification of newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE).

Methods: This study measured MR-proANP prospectively collected within 24 hours after symptom-onset in patients with AIS from the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study. Primary outcomes were CE stroke etiology and NDAF after prolonged cardiac monitoring, as well as a composite outcome of MACE (recurrent cerebrovascular events, myocardial infarction, or cardiovascular death) within 1 year. Logistic/Poisson and subproportional hazard regression were applied to evaluate the association between MR-proANP levels and outcomes. Additionally, a model for prediction of NDAF was derived and validated as a decision tool for immediate clinical application.

Results: Between October 1, 2014, and October 31, 2017, this study recruited 1,759 patients. Log₁₀MR-proANP levels were associated with CE stroke (OR: 7.96; 95% CI: 4.82-13.14; risk ratio: 3.12; 95% CI: 2.23-4.37), as well as NDAF (OR: 35.3; 95% CI: 17.58-71.03; risk ratio: 11.47; 95% CI: 6.74-19.53), and MACE (subdistributional HR: 2.02; 95% CI: 1.32-3.08) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81 (95% CI: 0.76-0.86), was well calibrated (calibration in the large: -0.086; calibration slope 1.053), and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA₂DS₂-VASc [Congestive Heart Failure, Hypertension, Age ≥65 or ≥75, Diabetes, Prior Cardioembolic Event, (female) Sex, or Vascular Disease] score).

Conclusions: MR-proANP is a valid biomarker to determine risk of NDAF and MACE in patients with AIS and can be used as a decision tool to identify patients for prolonged cardiac monitoring. (Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL study [BIOSIGNAL]; NCT02274727).

Keywords: atrial fibrillation; biomarker; ischemic stroke; midregional pro-atrial natriuretic peptide; risk prediction; stroke etiology.

Publication types

Multicenter Study

MeSH terms

Atrial Fibrillation* / complications
Atrial Fibrillation* / diagnosis
Atrial Natriuretic Factor* / analysis
Biomarkers
Cohort Studies
Humans
Ischemic Stroke* / diagnosis
Ischemic Stroke* / etiology
Risk Assessment

Substances

Biomarkers
Atrial Natriuretic Factor

Associated data

ClinicalTrials.gov/NCT02274727