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. 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: markus.arnold@usz.ch. 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.
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).
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).