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1. Sex differences of vascular brain lesions in patients with atrial fibrillation

Author

Christian Müller, Leo H Bonati, Pascal Meyre, Steffen Blum, Stefanie Aeschbacher, David Conen, Stefan Osswald, Urs Fischer, Manuel R Blum, Simon Jung, Jens Wuerfel, Christian Sticherling, Michael Kuhne, Philipp Krisai, Matthias Schwenkglenks, Luise Adam, Elisavet Moutzouri, Martin Feller, Nathalie Schwab, Claudio Schneider, Drahomir Aujesky, Nicolas Rodondi, Karl-Olof Lovblad, Michael Amann, Richard Kobza, Marie Méan, Andreas Müller, Giorgio Moschovitis, Fabienne Witassek, Silke Küest, Sonja Meier, Jürg-Hans Beer, Damiana Rakovic, Michael Coslovsky, Tiziano Moccetti, Ramun Schmid, Augusto Gallino, Carole Elodie Aubert, Georg Ehret, Angelo Auricchio, Giulio Conte, Daniel Hayoz, Benjamin Berte, Nathalie Lauriers, Peter Ammann, François Regoli, Dipen Shah, Laurent Roten, Marco Düring, Pascal Benkert, Simone Evers-Dörpfeld, Elisa Hennings, Ceylan Eken, Selinda Ceylan, Anne Springer, Heinrich Mattle, Tim Sinnecker, Leo Bonati, Anna Altermatt, Manuel Blum, Sacha Niederberger, Chloé Auberson, Simone Evers-Doerpfeld, Marc Girod, Elena Herber, Vasco Iten, Mirko Lischer, Christine Meyer-Zürn, Andreas U Monsch, Thomas Szucs, Gian Völlmin, Juerg Fuhrer, Axel Loewe, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Rylana Wenger, Christopher Beynon, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Simone Fontana, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Giulia Montrasio, Stefanie Leuenberger, Franziska Rutz, Adriana Anesini, Cristina Camporini, Maria Luce Caputo, Roman Brenner, David Altmann, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Martine Rime, Virgina Justi, Frauke Kellner-Weldon, Brigitta Mehmann, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Melanie Zbinden, Luisa Vicari, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Patrick Perret, Philippe Tavel, Cheryl Teres, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Jane Frangi-Kultalahti, Marcello Di Valentino, Jens Würfel, Petra Huber, Esther Ruberte, Vanessa Zuber, Gilles Dutilh, Milica Markovic, Pia Neuschwander, and Patrick Simon

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective To examine sex differences in prevalence, volume and distribution of vascular brain lesions on MRI among patients with atrial fibrillation (AF).Methods In this cross-sectional analysis, we included 1743 patients with AF (27% women) from the multicentre Swiss Atrial Fibrillation study (SWISS-AF) with available baseline brain MRI. We compared presence and total volume of large non-cortical or cortical infarcts (LNCCIs), small non-cortical infarcts, microbleeds (MB) and white matter hyperintensities (WMH, Fazekas score ≥2 for moderate or severe degree) between men and women with multivariable logistic regression. We generated voxel-based probability maps to assess the anatomical distribution of lesions.Results We found no strong evidence for an association of female sex with the prevalence of all ischaemic infarcts (LNCCI and SNCI combined; adjusted OR 0.86, 95% CI 0.67 to 1.09, p=0.22), MB (adjusted OR 0.91, 95% CI 0.68 to 1.21, p=0.52) and moderate or severe WMH (adjusted OR 1.15, 95% CI 0.90 to 1.48, p=0.27). However, total WMH volume was 17% larger among women than men (multivariable adjusted multiplicative effect 1.17, 95% CI 1.01 to 1.35; p=0.04). Lesion probability maps showed a right hemispheric preponderance of ischaemic infarcts in both men and women, while WMH were distributed symmetrically.Conclusion Women had higher white matter disease burden than men, while volume and prevalence of other lesions did not differ. Our findings highlight the importance of controlling risk factors for cerebral small vessel disease in patients with AF, especially among women.

Published
2022
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2. Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation

Author

Steffen Blum, Stefanie Aeschbacher, Pascal Meyre, Michael Kühne, Nicolas Rodondi, Jürg H. Beer, Peter Ammann, Giorgio Moschovitis, Leo H. Bonati, Manuel R. Blum, Peter Kastner, Fiona Baguley, Christian Sticherling, Stefan Osswald, David Conen, Chloé Auberson, Leo Bonati, Selinda Ceylan, Simone Doerpfeld, Ceylan Eken, Marc Girod, Peter Hämmerle, Philipp Krisai, Christine Meyer-Zürn, Andreas U. Monsch, Christian Müller, Anne Springer, Thomas Szucs, Gian Voellmin, Leon Zwimpfer, Drahomir Aujesky, Urs Fischer, Juerg Fuhrer, Laurent Roten, Simon Jung, Heinrich Mattle, Luise Adam, Carole Elodie Aubert, Martin Feller, Axel Loewe, Elisavet Moutzouri, Claudio Schneider, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Damiana Rakovic, Nathalie Schwab, Rylana Wenger, Christopher Beynon, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Andreas Müller, Simone Fontana, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Giulia Montrasio, Stefanie Leuenberger, Franziska Rutz, Jürg-Hans Beer, Angelo Auricchio, Adriana Anesini, Cristina Camporini, Giulio Conte, Maria Luce Caputo, Francois Regoli, Tiziano Moccetti, Roman Brenner, David Altmann, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Martine Rime, Daniel Hayoz, Benjamin Berte, Virgina Justi, Frauke Kellner-Weldon, Brigitta Mehmann, Sonja Meier, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Melanie Zbinden, Richard Kobza, Jane Frangi-Kultalahti, Anica Pin, Luisa Vicari, Georg Ehret, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Philippe Tavel, Cheryl Teres, Dipen Shah, Nathalie Lauriers, Marie Méan, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Augusto Gallino, Marcello Di Valentino, Fabienne Witassek, Matthias Schwenkglenks, Jens Würfel, Anna Altermatt, Michael Amann, Petra Huber, Esther Ruberte, Tim Sinnecker, Vanessa Zuber, Michael Coslovsky, Pascal Benkert, Gilles Dutilh, Milica Markovic, Patrick Simon, Ramun Schmid, Clinical sciences, Auberson, Chloé, Bonati, Leo, Ceylan, Selinda, Doerpfeld, Simone, Eken, Ceylan, Girod, Marc, Hämmerle, Peter, Krisai, Philipp, Meyer-Zürn, Christine, Monsch, Andreas U., Müller, Christian, Springer, Anne, Szucs, Thomas, Voellmin, Gian, Zwimpfer, Leon, Aujesky, Drahomir, Fischer, Urs, Fuhrer, Juerg, Roten, Laurent, Jung, Simon, Mattle, Heinrich, Adam, Luise, Aubert, Carole Elodie, Feller, Martin, Loewe, Axel, Moutzouri, Elisavet, Schneider, Claudio, Flückiger, Tanja, Groen, Cindy, Ehrsam, Lukas, Hellrigl, Sven, Nuoffer, Alexandra, Rakovic, Damiana, Schwab, Nathalie, Wenger, Rylana, Beynon, Christopher, Dillier, Roger, Deubelbeiss, Michèle, Eberli, Franz, Franzini, Christine, Juchli, Isabel, Liedtke, Claudia, Nadler, Jacqueline, Obst, Thayze, Roth, Jasmin, Schlomowitsch, Fiona, Schneider, Xiaoye, Studerus, Katrin, Tynan, Noreen, Weishaupt, Dominik, Müller, Andreas, Fontana, Simone, Kuest, Silke, Scheuch, Karin, Hischier, Denise, Bonetti, Nicole, Grau, Alexandra, Villinger, Jonas, Laube, Eva, Baumgartner, Philipp, Filipovic, Mark, Frick, Marcel, Montrasio, Giulia, Leuenberger, Stefanie, Rutz, Franziska, Auricchio, Angelo, Anesini, Adriana, Camporini, Cristina, Conte, Giulio, Caputo, Maria Luce, Regoli, Francois, Moccetti, Tiziano, Brenner, Roman, Altmann, David, Gemperle, Michaela, Firmann, Mathieu, Foucras, Sandrine, Rime, Martine, Hayoz, Daniel, Berte, Benjamin, Justi, Virgina, Kellner-Weldon, Frauke, Mehmann, Brigitta, Meier, Sonja, Roth, Myriam, Ruckli-Kaeppeli, Andrea, Russi, Ian, Schmidt, Kai, Young, Mabelle, Zbinden, Melanie, Kobza, Richard, Frangi-Kultalahti, Jane, Pin, Anica, Vicari, Luisa, Ehret, Georg Benedikt, Gallet, Hervé, Guillermet, Elise, Lazeyras, François, Lövblad, Karl-Olof, Perret, Patrick, Tavel, Philippe, Teres Castillo, Cheryl, Shah, Dipen, Lauriers, Nathalie, Méan, Marie, Salzmann, Sandrine, Schläpfer, Jürg, Grêt, Andrea, Novak, Jan, Vitelli, Sandra, Stephan, Frank-Peter, Gallino, Augusto, Di Valentino, Marcello, Witassek, Fabienne, Schwenkglenks, Matthias, Würfel, Jens, Altermatt, Anna, Amann, Michael, Huber, Petra, Ruberte, Esther, Sinnecker, Tim, Zuber, Vanessa, Coslovsky, Michael, Benkert, Pascal, Dutilh, Gilles, Markovic, Milica, Simon, Patrick, and Schmid, Ramun

Subjects
Male, medicine.medical_specialty, medicine.drug_class, Epidemiology, Heart failure, 030204 cardiovascular system & hematology, ddc:616.0757, 03 medical and health sciences, 0302 clinical medicine, Insulin-Like Growth Factor Binding Proteins/blood, Physiology (medical), Internal medicine, Atrial Fibrillation, Clinical endpoint, Natriuretic peptide, medicine, Heart Failure/blood, Humans, 030212 general & internal medicine, cardiovascular diseases, Hospitalization/statistics & numerical data, Aged, Retrospective Studies, ddc:616, Heart Failure, Proportional hazards model, business.industry, Insulin-like growth factor-binding protein 7, Hazard ratio, Atrial fibrillation, Middle Aged, medicine.disease, Prognosis, Confidence interval, Hospitalization, Insulin-Like Growth Factor Binding Proteins, Atrial Fibrillation/blood, Cardiology, Disease Progression, Female, business, Cardiology and Cardiovascular Medicine, Biomarkers/blood, Biomarkers, Cohort study, Follow-Up Studies
Abstract

BACKGROUND: The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE: The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS: We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. RESULTS: Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend

Published
2020

3. Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation

Author

David Conen, Nicolas Rodondi, Andreas Müller, Juerg H. Beer, Peter Ammann, Giorgio Moschovitis, Angelo Auricchio, Daniel Hayoz, Richard Kobza, Dipen Shah, Jan Novak, Jürg Schläpfer, Marcello Di Valentino, Stefanie Aeschbacher, Steffen Blum, Pascal Meyre, Christian Sticherling, Leo H. Bonati, Georg Ehret, Elisavet Moutzouri, Urs Fischer, Andreas U. Monsch, Christoph Stippich, Jens Wuerfel, Tim Sinnecker, Michael Coslovsky, Matthias Schwenkglenks, Michael Kühne, Stefan Osswald, Sebastian Berger, Raffaele Bernasconi, Lorin Fröhlich, Tobias Göldi, Rebecca Gugganig, Thomas Kofler, Philipp Krisai, Michel Mongiat, Christiane Pudenz, Javier Ruperti Repilado, Aleksandra Schweizer, Anne Springer, Samuel Stempfel, Thomas Szucs, Jan van der Stouwe, Gian Voellmin, Leon Zwimpfer, Drahomir Aujesky, Juerg Fuhrer, Laurent Roten, Simon Jung, Heinrich Mattle, Luise Adam, Carole Elodie Aubert, Martin Feller, Claudio Schneider, Axel Loewe, Tanja Flückiger, Cindy Groen, Nathalie Schwab, Christopher Beynon, Roger Dillier, Franz Eberli, Simone Fontana, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Xiaoye Schneider, Katrin Studerus, Dominik Weishaupt, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Corina Bello, Henriette Isberg, Alexandra Grau, Jonas Villinger, Mary-Monica Papaux, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Adriana Anesini, Cristina Camporini, Giulio Conte, Maria Luce Caputo, Francois Regoli, Tiziano Moccetti, Roman Brenner, David Altmann, Manuela Forrer, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Benjamin Berte, Andrea Kaeppeli, Brigitta Mehmann, Markus Pfeiffer, Ian Russi, Kai Schmidt, Vanessa Weberndoerfer, Mabelle Young, Melanie Zbinden, Luisa Vicari, Jane Frangi, Tatiana Terrot, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Cheryl Teres, Nathalie Lauriers, Marie Méan, Sandrine Salzmann, Nisha Arenja, Andrea Grêt, Sandra Vitelli, Augusto Gallino, Renate Schoenenberger-Berzins, Fabienne Witassek, Ernst-Wilhelm Radue, Pascal Benkert, Thomas Fabbro, Patrick Simon, Ramun Schmid, Clinical sciences, Gallet, Hervé, Guillermet, Elise, Lazeyras, François, Lövblad, Karl-Olof, Perret, Patrick, Teres Castillo, Cheryl, University of Zurich, and Conen, David

Subjects
Male, 030204 cardiovascular system & hematology, Neuropsychological Tests, Magnetic Resonance Imaging/methods, 0302 clinical medicine, Cognition, Risk Factors, Atrial Fibrillation, Silent cerebral infarcts, 030212 general & internal medicine, Prospective Studies, Cognitive decline, Stroke, Cognition/physiology, ddc:616, Montreal Cognitive Assessment, Brain, Atrial fibrillation, Cerebral Infarction, Cerebral Infarction/complications, Magnetic Resonance Imaging, Cognitive test, Cardiology, Microbleeds, Female, Cardiology and Cardiovascular Medicine, Atrial Fibrillation/complications, medicine.medical_specialty, Cognitive Dysfunction/diagnosis, 610 Medicine & health, macromolecular substances, 11171 Cardiocentro Ticino, 2705 Cardiology and Cardiovascular Medicine, White matter lesions, 03 medical and health sciences, Cognitive dysfunction, 10043 Clinic for Neuroradiology, Internal medicine, medicine, Humans, Brain/pathology, Cognitive Dysfunction, Aged, business.industry, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), medicine.disease, Confidence interval, Hyperintensity, Institutional repository, business, Follow-Up Studies
Abstract

BACKGROUND Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions. OBJECTIVES This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF. METHODS Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack. RESULTS The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001). CONCLUSIONS Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

Published
2018

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