Plasma β-Thromboglobulin Is Inversely Associated With Cerebral Microbleeds in Atrial Fibrillation

Benedict C Kupper¹, Martin F Reiner², Laura Werlen³, Stefanie Aeschbacher^{4

5}, Pratintip Lee⁶, Meret Allemann⁶, Giorgio Moschovitis⁷, Thomas Lüscher^{8

9}, Giovanni G Camici⁸, Nicolas Rodondi^{10

11}, Luise Adam^{10

12}, Pascal B Meyre^{4

5}, Leo H Bonati^{13

14}, Tim Sinnecker^{13

15}, Michael Kühne^{4

5}, Stefan Osswald^{4

5}, David Conen¹⁶, Jürg H Beer^{1

6}; Swiss-AF Investigators

Affiliations

¹ Department of Internal Medicine, Cantonal Hospital of Baden, Switzerland (B.C.K., J.H.B.).
² Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland (M.F.R.).
³ Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland. (L.W.).
⁴ Cardiology Division, Department of Medicine, University Hospital Basel, University of Basel, Switzerland. (S.A., P.B.M., M.K., S.O.).
⁵ Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Switzerland. (S.A., P.B.M., M.K., S.O.).
⁶ Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, Switzerland. (P.L., M.A., J.H.B.).
⁷ Cardiology Division, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Switzerland (G.M.).
⁸ Center for Molecular Cardiology, University of Zurich, Switzerland. (T.L., G.G.C.).
⁹ Heart Division, Royal Brompton, and Harefield Hospitals, Cardiovascular Academic Group, King's College, London (T.L.).
¹⁰ Institute of Primary Health Care (BIHAM), University of Bern, Switzerland. (N.R., L.A.).
¹¹ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. (N.R.).
¹² Angiology Department, Cantonal Hospital of Schaffhausen, Switzerland (L.A.).
¹³ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Switzerland. (L.H.B., T.S.).
¹⁴ Research Department, Reha Rheinfelden, Switzerland (L.H.B.).
¹⁵ Medical Image Analysis Center (MIAC AG) Basel, Switzerland (T.S.).
¹⁶ Population Health Research Institute, McMaster University, Hamilton, Canada (D.C.).

PMID: 40959897
DOI: 10.1161/STROKEAHA.124.049972

Plasma β-Thromboglobulin Is Inversely Associated With Cerebral Microbleeds in Atrial Fibrillation

Benedict C Kupper et al. Stroke. 2025.

. 2025 Sep 17.

doi: 10.1161/STROKEAHA.124.049972. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, Cantonal Hospital of Baden, Switzerland (B.C.K., J.H.B.).
² Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland (M.F.R.).
³ Department of Clinical Research, University Hospital Basel, University of Basel, Switzerland. (L.W.).
⁴ Cardiology Division, Department of Medicine, University Hospital Basel, University of Basel, Switzerland. (S.A., P.B.M., M.K., S.O.).
⁵ Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Switzerland. (S.A., P.B.M., M.K., S.O.).
⁶ Laboratory for Platelet Research, Center for Molecular Cardiology, University of Zurich, Switzerland. (P.L., M.A., J.H.B.).
⁷ Cardiology Division, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Switzerland (G.M.).
⁸ Center for Molecular Cardiology, University of Zurich, Switzerland. (T.L., G.G.C.).
⁹ Heart Division, Royal Brompton, and Harefield Hospitals, Cardiovascular Academic Group, King's College, London (T.L.).
¹⁰ Institute of Primary Health Care (BIHAM), University of Bern, Switzerland. (N.R., L.A.).
¹¹ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland. (N.R.).
¹² Angiology Department, Cantonal Hospital of Schaffhausen, Switzerland (L.A.).
¹³ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Switzerland. (L.H.B., T.S.).
¹⁴ Research Department, Reha Rheinfelden, Switzerland (L.H.B.).
¹⁵ Medical Image Analysis Center (MIAC AG) Basel, Switzerland (T.S.).
¹⁶ Population Health Research Institute, McMaster University, Hamilton, Canada (D.C.).

PMID: 40959897
DOI: 10.1161/STROKEAHA.124.049972

Abstract

Background: Biomarkers may increase the understanding of the pathophysiology of brain lesions in newly evaluated atrial fibrillation. BTG (β-thromboglobulin) is released from platelet alpha granules upon activation, reflecting platelet activation and destruction. We assessed the association of plasma BTG with cerebral microbleeds (CMBs) and ischemic brain lesions using brain magnetic resonance imaging (bMRI) in patients with atrial fibrillation.

Methods: BTG was analyzed using the Luminex assay. CMBs and ischemic brain lesions were detected by standardized bMRI of 1724 patients from the Swiss-Atrial Fibrillation cohort, a prospective, national, multicenter cohort study that enrolled patients between 2014 and 2017. For this cross-sectional analysis, associations of BTG with bMRI lesions were evaluated by logistic and linear regression analyses using 2 models. The first model was adjusted for age and sex, and the second model was additionally multivariable-adjusted for a large number of clinical characteristics, including coronary artery disease, hypertension, diabetes, chronic kidney disease, history of heart failure, major bleeding, as well as concomitant platelet inhibitor, and anticoagulation therapy.

Results: Mean age at baseline was 72.5 years (SD, 8.4), and 27.3% were female. On bMRI, CMBs were found in 369 patients (21.4%) and cerebral infarcts in 635 (36.8%). After multivariable adjustment, a 1-unit increase of log-transformed plasma BTG was associated with 25% lower odds of having CMBs (odds ratio, 0.75 [95% CI, 0.59-0.96]). However, BTG was not associated with the presence of large noncortical or cortical infarcts (odds ratio, 0.85 [95% CI, 0.66-1.09]) or small noncortical infarcts (odds ratio, 1.06 [95% CI, 0.83-1.35]).

Conclusions: In patients with atrial fibrillation, the platelet-specific biomarker BTG was inversely and independently associated with CMBs on bMRI. Low-grade platelet activation may improve vascular integrity.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02105844.

Keywords: anticoagulants; atrial fibrillation; heart failure; magnetic resonance imaging; platelet activation.

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Plasma β-Thromboglobulin Is Inversely Associated With Cerebral Microbleeds in Atrial Fibrillation

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Plasma β-Thromboglobulin Is Inversely Associated With Cerebral Microbleeds in Atrial Fibrillation

Authors

Affiliations

Abstract

Associated data

LinkOut - more resources

Full Text Sources

Medical