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4. Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach

Author

Serra-Burriel, Miquel, Aebersold, Helena, Foster-Witassek, Fabienne, Coslovsky, Michael, Rodondi, Nicolas, Blum, Manuel R., Sticherling, Christian, Moschovitis, Giorgio, Beer, Jürg H., Reichlin, Tobias, Krisai, Philipp, Aeschbacher, Stefanie, Paladini, Rebecca E., Kühne, Michael, Osswald, Stefan, Conen, David, Felder, Stefan, and Schwenkglenks, Matthias

Published
2023
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8. Long-term risk of adverse outcomes according to atrial fibrillation type

Author

Blum, Steffen, Aeschbacher, Stefanie, Coslovsky, Michael, Meyre, Pascal B., Reddiess, Philipp, Ammann, Peter, Erne, Paul, Moschovitis, Giorgio, Di Valentino, Marcello, Shah, Dipen, Schläpfer, Jürg, Müller, Rahel, Beer, Jürg H., Kobza, Richard, Bonati, Leo H., Moutzouri, Elisavet, Rodondi, Nicolas, Meyer-Zürn, Christine, Kühne, Michael, Sticherling, Christian, Osswald, Stefan, and Conen, David

Published
2022
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9. Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020

Author

Gebhard, Caroline E, Sütsch, Claudia, Gebert, Pimrapat, Gysi, Bianca, Bengs, Susan, Todorov, Atanas, Deforth, Manja, Buehler, Philipp K, Meisel, Alexander, Schuepbach, Reto A, Zinkernagel, Annelies S, Brugger, Silvio D, Acevedo, Claudio, Patriki, Dimitri, Wiggli, Benedikt, Beer, Jürg H, Friedl, Andrée, Twerenbold, Raphael, Kuster, Gabriela M, Pargger, Hans, Tschudin-Sutter, Sarah, Schefold, Joerg C, Spinetti, Thibaud, Henze, Chiara, Pasqualini, Mina, Sager, Dominik F, Mayrhofer, Lilian, Grieder, Mirjam, Tontsch, Janna, Franzeck, Fabian C, et al, Gebhard, Caroline E, Sütsch, Claudia, Gebert, Pimrapat, Gysi, Bianca, Bengs, Susan, Todorov, Atanas, Deforth, Manja, Buehler, Philipp K, Meisel, Alexander, Schuepbach, Reto A, Zinkernagel, Annelies S, Brugger, Silvio D, Acevedo, Claudio, Patriki, Dimitri, Wiggli, Benedikt, Beer, Jürg H, Friedl, Andrée, Twerenbold, Raphael, Kuster, Gabriela M, Pargger, Hans, Tschudin-Sutter, Sarah, Schefold, Joerg C, Spinetti, Thibaud, Henze, Chiara, Pasqualini, Mina, Sager, Dominik F, Mayrhofer, Lilian, Grieder, Mirjam, Tontsch, Janna, Franzeck, Fabian C, and et al

Abstract

Background: Women are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown. Aim: We assessed the impact of sex and gender on PASC in a Swiss population. Method: Our multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030). Conclusion: Specific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Published
2024

12. Omega-3 Fatty Acids and Markers of Thrombosis in Patients with Atrial Fibrillation

Author

Reiner, Martin F., primary, Bertschi, Daniela A., additional, Werlen, Laura, additional, Wiencierz, Andrea, additional, Aeschbacher, Stefanie, additional, Lee, Pratintip, additional, Rodondi, Nicolas, additional, Moutzouri, Elisavet, additional, Bonati, Leo, additional, Reichlin, Tobias, additional, Moschovitis, Giorgio, additional, Rutishauser, Jonas, additional, Kühne, Michael, additional, Osswald, Stefan, additional, Conen, David, additional, and Beer, Jürg H., additional

Published
2024
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13. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Author

Weiner, January, 3rd, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T, Lippert, Lena J, Stubbemann, Paula, Real, Luis M, Macías, Juan, Pineda, Juan A, Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H., Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M, Mühlemann, Barbara, Arjun Arkal, Rao, Fragiadakis, Gabriela K., Mick, Eran, COMET, Consortium, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn M., Kangelaris, Kirsten N., Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C, Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Pa-COVID, Study Group, Ripke, Stephan, Sander, Leif E, Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, and Heidecker, Bettina

Published
2021
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17. Insulin-like growth factor-binding protein 7 and risk of congestive heart failure hospitalization in patients with atrial fibrillation

Author

Aeschbacher, Stefanie, Auberson, Chloé, Blum, Steffen, Bonati, Leo, Ceylan, Selinda, Conen, David, Doerpfeld, Simone, Eken, Ceylan, Girod, Marc, Hämmerle, Peter, Krisai, Philipp, Kühne, Michael, Meyer-Zürn, Christine, Meyre, Pascal, Monsch, Andreas U., Müller, Christian, Osswald, Stefan, Springer, Anne, Sticherling, Christian, 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, Rodondi, Nicolas, 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, Beer, Jürg-Hans, Auricchio, Angelo, Anesini, Adriana, Camporini, Cristina, Conte, Giulio, Caputo, Maria Luce, Regoli, Francois, Moccetti, Tiziano, Brenner, Roman, Altmann, David, Gemperle, Michaela, Ammann, Peter, 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, Moschovitis, Giorgio, Ehret, Georg, Gallet, Hervé, Guillermet, Elise, Lazeyras, Francois, Lovblad, Karl-Olof, Perret, Patrick, Tavel, Philippe, Teres, 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, Schmid, Ramun, Beer, Jürg H., Bonati, Leo H., Blum, Manuel R., Kastner, Peter, and Baguley, Fiona

Published
2021
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19. Sirt6 deletion in bone marrow-derived cells increases atherosclerosis – Central role of macrophage scavenger receptor 1

Author

Arsiwala, Tasneem, Pahla, Jürgen, van Tits, Lambertus J., Bisceglie, Lavinia, Gaul, Daniel S., Costantino, Sarah, Miranda, Melroy X., Nussbaum, Kathrin, Stivala, Simona, Blyszczuk, Przemyslaw, Weber, Julien, Tailleux, Anne, Stein, Sokrates, Paneni, Francesco, Beer, Jürg H., Greter, Melanie, Becher, Burkhard, Mostoslavsky, Raul, Eriksson, Urs, Staels, Bart, Auwerx, Johan, Hottiger, Michael O., Lüscher, Thomas F., and Matter, Christian M.

Published
2020
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20. Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging

Author

Saeedi Saravi, Seyed Soheil, primary, Pugin, Benoit, additional, Constancias, Florentin, additional, Thomas, Aurélien, additional, Gludic, Sylvain Le, additional, Allemann, Meret Sarah, additional, Karsai, Gergely, additional, Lee, Pratintip, additional, Menni, Cristina, additional, Attaye, Ilias, additional, and Beer, Jürg H., additional

Published
2023
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24. Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation

Author

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

Published
2019
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25. Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

Author

Gebhard, Caroline E., Sütsch, Claudia, Gebert, Pimrapat, Gysi, Bianca, Bengs, Susan, Todorov, Atanas, Deforth, Manja, Buehler, Philipp K., Meisel, Alexander, Schuepbach, Reto A., Zinkernagel, Annelies S., Brugger, Silvio D., Acevedo, Claudio, Patriki, Dimitri, Wiggli, Benedikt, Beer, Jürg H., Friedl, Andrée, Twerenbold, Raphael, Kuster, Gabriela M., and Pargger, Hans

Published
2024
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27. Blood Pressure and Brain Lesions in Patients With Atrial Fibrillation

Author

Aeschbacher, Stefanie, Blum, Steffen, Meyre, Pascal B., Coslovsky, Michael, Vischer, Annina S., Sinnecker, Tim, Rodondi, Nicolas, Beer, Jürg H., Moschovitis, Giorgio, Moutzouri, Elisavet, Hunkeler, Christof, Burkard, Thilo, Eken, Ceylan, Roten, Laurent, Zuern, Christine S., Sticherling, Christian, Wuerfel, Jens, Bonati, Leo H., Conen, David, Osswald, Stefan, and Kühne, Michael

Published
2021
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28. Association of Statin Use and Lipid Levels with Cerebral Microbleeds and Intracranial Hemorrhage in Patients with Atrial Fibrillation: a Prospective Cohort Study

Author

Moutzouri, Elisavet, primary, Glutz, Matthias, additional, Abolhassani, Nazanin, additional, Feller, Martin, additional, Adam, Luise, additional, Gencer, Baris, additional, Del Giovane, Cinzia, additional, Bétrisey, Sylvain, additional, Paladini, Rebecca E., additional, Hennings, Elisa, additional, Aeschbacher, Stefanie, additional, Beer, Jürg H., additional, Moschovitis, Giorgio, additional, Seiffge, David J, additional, De Marchis, Gian Marco, additional, Coslovsky, Michael, additional, Tobias, Reichlin, additional, Conte, Giulio, additional, Sinnecker, Tim, additional, Schwenkglenks, Matthias, additional, Bonati, Leo H., additional, Kastner, Peter, additional, Aujesky, Drahomir Antonin, additional, Kühne, Michael, additional, Osswald, Stefan, additional, Fischer, Urs, additional, Conen, David, additional, and Rodondi, Nicolas, additional

Published
2023
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29. Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction

Author

Saravi, Seyed Soheil Saeedi, primary, Bonetti, Nicole R., additional, Vukolic, Ana, additional, Vdovenko, Daria, additional, Lee, Pratintip, additional, Liberale, Luca, additional, Basso, Cristina, additional, Rizzo, Stefania, additional, Akhmedov, Alexander, additional, Lüscher, Thomas F., additional, Camici, Giovanni G., additional, and Beer, Jürg H., additional

Published
2023
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30. Bone Morphogenetic Protein 10—A Novel Biomarker to Predict Adverse Outcomes in Patients With Atrial Fibrillation

Author

Hennings, Elisa; https://orcid.org/0000-0003-2616-5535, Blum, Steffen; https://orcid.org/0000-0002-0325-8993, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Knecht, Sven; https://orcid.org/0000-0001-7122-021X, Eken, Ceylan, Lischer, Mirko; https://orcid.org/0000-0001-7088-2801, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Krisai, Philipp; https://orcid.org/0000-0002-4367-2363, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Ammann, Peter, Conte, Giulio; https://orcid.org/0000-0003-2248-3456, De Perna, Maria Luisa; https://orcid.org/0000-0003-1171-7640, Kobza, Richard; https://orcid.org/0000-0003-3988-7262, Blum, Manuel R, Bossard, Matthias; https://orcid.org/0000-0002-8290-661X, Kastner, Peter; https://orcid.org/0000-0001-8744-7152, Ziegler, André; https://orcid.org/0000-0002-9838-8087, Müller, Christian; https://orcid.org/0000-0002-1120-6405, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Pfister, Otmar; https://orcid.org/0000-0002-6155-5494, Zuern, Christine S; https://orcid.org/0000-0001-6625-284X, Conen, David; https://orcid.org/0000-0002-2459-5251, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Hennings, Elisa; https://orcid.org/0000-0003-2616-5535, Blum, Steffen; https://orcid.org/0000-0002-0325-8993, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Knecht, Sven; https://orcid.org/0000-0001-7122-021X, Eken, Ceylan, Lischer, Mirko; https://orcid.org/0000-0001-7088-2801, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Krisai, Philipp; https://orcid.org/0000-0002-4367-2363, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Ammann, Peter, Conte, Giulio; https://orcid.org/0000-0003-2248-3456, De Perna, Maria Luisa; https://orcid.org/0000-0003-1171-7640, Kobza, Richard; https://orcid.org/0000-0003-3988-7262, Blum, Manuel R, Bossard, Matthias; https://orcid.org/0000-0002-8290-661X, Kastner, Peter; https://orcid.org/0000-0001-8744-7152, Ziegler, André; https://orcid.org/0000-0002-9838-8087, Müller, Christian; https://orcid.org/0000-0002-1120-6405, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Pfister, Otmar; https://orcid.org/0000-0002-6155-5494, Zuern, Christine S; https://orcid.org/0000-0001-6625-284X, Conen, David; https://orcid.org/0000-0002-2459-5251, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, and Osswald, Stefan; https://orcid.org/0000-0002-9240-6731

Abstract

Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). We aimed to assess the predictive value of the novel atrial‐specific biomarker BMP10 (bone morphogenetic protein 10) for death and MACE in patients with AF in comparison with NT‐proBNP (N‐terminal prohormone of B‐type natriuretic peptide). Methods and Results BMP10 and NT‐proBNP were measured in patients with AF enrolled in Swiss‐AF (Swiss Atrial Fibrillation Study), a prospective multicenter cohort study. A total of 2219 patients were included (median follow‐up 4.3 years [interquartile range 3.9, 5.1], mean age 73±9 years, 73% male). In multivariable Cox proportional hazard models, the adjusted hazard ratio (aHR) associated with 1 ng/mL increase of BMP10 was 1.60 (95% CI, 1.37–1.87) for all‐cause death, and 1.54 (95% CI, 1.35–1.76) for MACE. For all‐cause death, the concordance index was 0.783 (95% CI, 0.763–0.809) for BMP10, 0.784 (95% CI, 0.765–0.810) for NT‐proBNP, and 0.789 (95% CI, 0.771–0.815) for both biomarkers combined. For MACE, the concordance index was 0.732 (95% CI, 0.715–0.754) for BMP10, 0.747 (95% CI, 0.731–0.768) for NT‐proBNP, and 0.750 (95% CI, 0.734–0.771) for both biomarkers combined. When grouping patients according to NT‐proBNP categories (<300, 300–900, >900 ng/L), higher aHRs were observed in patients with high BMP10 in the categories of low NT‐proBNP (all‐cause death aHR, 2.28 [95% CI, 1.15–4.52], MACE aHR, 1.88 [95% CI, 1.07–3.28]) and high NT‐proBNP (all‐cause death aHR, 1.61 [95% CI, 1.14–2.26], MACE aHR, 1.38 [95% CI, 1.07–1.80]). Conclusions BMP10 strongly predicted all‐cause death and MACE in patients with AF. BMP10 provided additional prognostic information in low‐ and high‐risk patients according to NT‐proBNP stratification. Registration https://www.clinicaltrials.gov ; Unique identifier: NCT02105844.

Published
2023

31. Targeting the redox system for cardiovascular regeneration in aging

Author

Allemann, Meret Sarah, Lee, Pratintip, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Saeedi Saravi, Seyed Soheil; https://orcid.org/0000-0001-6227-8049, Allemann, Meret Sarah, Lee, Pratintip, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, and Saeedi Saravi, Seyed Soheil; https://orcid.org/0000-0001-6227-8049

Abstract

Cardiovascular aging presents a formidable challenge, as the aging process can lead to reduced cardiac function and heightened susceptibility to cardiovascular diseases. Consequently, there is an escalating, unmet medical need for innovative and effective cardiovascular regeneration strategies aimed at restoring and rejuvenating aging cardiovascular tissues. Altered redox homeostasis and the accumulation of oxidative damage play a pivotal role in detrimental changes to stem cell function and cellular senescence, hampering regenerative capacity in aged cardiovascular system. A mounting body of evidence underscores the significance of targeting redox machinery to restore stem cell self-renewal and enhance their differentiation potential into youthful cardiovascular lineages. Hence, the redox machinery holds promise as a target for optimizing cardiovascular regenerative therapies. In this context, we delve into the current understanding of redox homeostasis in regulating stem cell function and reprogramming processes that impact the regenerative potential of the cardiovascular system. Furthermore, we offer insights into the recent translational and clinical implications of redox-targeting compounds aimed at enhancing current regenerative therapies for aging cardiovascular tissues.

Published
2023

32. Omega‐3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation

Author

Baumgartner, Philipp; https://orcid.org/0000-0003-1525-2019, Reiner, Martin F; https://orcid.org/0000-0002-9887-2469, Wiencierz, Andrea; https://orcid.org/0000-0001-8786-7915, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Bonetti, Nicole R, Filipovic, Mark G; https://orcid.org/0000-0001-6936-6041, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Zuern, Christine S; https://orcid.org/0000-0001-6625-284X, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Oberle, Jolanda; https://orcid.org/0000-0003-2988-3858, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Camici, Giovanni G; https://orcid.org/0000-0002-0523-0695, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Conen, David; https://orcid.org/0000-0002-2459-5251, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Baumgartner, Philipp; https://orcid.org/0000-0003-1525-2019, Reiner, Martin F; https://orcid.org/0000-0002-9887-2469, Wiencierz, Andrea; https://orcid.org/0000-0001-8786-7915, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Bonetti, Nicole R, Filipovic, Mark G; https://orcid.org/0000-0001-6936-6041, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Zuern, Christine S; https://orcid.org/0000-0001-6625-284X, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Oberle, Jolanda; https://orcid.org/0000-0003-2988-3858, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Camici, Giovanni G; https://orcid.org/0000-0002-0523-0695, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Conen, David; https://orcid.org/0000-0002-2459-5251, and Beer, Jürg H; https://orcid.org/0000-0002-7199-0406

Abstract

Background Previous randomized control trials showed mixed results concerning the effect of omega‐3 fatty acids (n‐3 FAs) on atrial fibrillation (AF). The associations of n‐3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n‐3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n‐3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha‐linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS‐AF (Swiss Atrial Fibrillation cohort). Individual and total n‐3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n‐3 FA (odds ratio [OR], 0.97 [95% CI, 0.89–1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82–1.06]), whereas other individual n‐3 FAs showed no association with nonparoxysmal AF. Higher total n‐3 FAs (estimate 0.99 [95% CI, 0.98–1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97–1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89–0.99]). Conclusions We found no strong evidence for an association of n‐3 FA blood levels with AF type, but higher total n‐3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.

Published
2023

33. Intravenously administered APAC, a dual AntiPlatelet AntiCoagulant, targets arterial injury site to inhibit platelet thrombus formation and tissue factor activity in mice

Author

Bonetti, Nicole R, Jouppila, Annukka S, Saeedi Saravi, Seyed Soheil, Cooley, Brian C, Pasterk, Lisa, Liberale, Luca L, Gobbato, Sara, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Camici, Giovanni G; https://orcid.org/0000-0002-0523-0695, Lassila, Riitta P, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Bonetti, Nicole R, Jouppila, Annukka S, Saeedi Saravi, Seyed Soheil, Cooley, Brian C, Pasterk, Lisa, Liberale, Luca L, Gobbato, Sara, Lüscher, Thomas F; https://orcid.org/0000-0002-5259-538X, Camici, Giovanni G; https://orcid.org/0000-0002-0523-0695, Lassila, Riitta P, and Beer, Jürg H; https://orcid.org/0000-0002-7199-0406

Published
2023

34. Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study

Author

Moutzouri, Elisavet; https://orcid.org/0000-0002-7713-7553, Glutz, Matthias, Abolhassani, Nazanin, Feller, Martin; https://orcid.org/0000-0003-2519-836X, Adam, Luise, Gencer, Baris; https://orcid.org/0000-0002-8954-9694, Del Giovane, Cinzia, Bétrisey, Sylvain, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Hennings, Elisa; https://orcid.org/0000-0003-2616-5535, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Seiffge, David, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Conte, Giulio, Sinnecker, Tim, Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Kastner, Peter, Aujesky, Drahomir; https://orcid.org/0000-0002-3970-2670, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Fischer, Urs; https://orcid.org/0000-0003-0521-4051, Conen, David; https://orcid.org/0000-0002-2459-5251, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Moutzouri, Elisavet; https://orcid.org/0000-0002-7713-7553, Glutz, Matthias, Abolhassani, Nazanin, Feller, Martin; https://orcid.org/0000-0003-2519-836X, Adam, Luise, Gencer, Baris; https://orcid.org/0000-0002-8954-9694, Del Giovane, Cinzia, Bétrisey, Sylvain, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Hennings, Elisa; https://orcid.org/0000-0003-2616-5535, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Seiffge, David, De Marchis, Gian Marco; https://orcid.org/0000-0002-0342-9780, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Conte, Giulio, Sinnecker, Tim, Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Kastner, Peter, Aujesky, Drahomir; https://orcid.org/0000-0002-3970-2670, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Fischer, Urs; https://orcid.org/0000-0003-0521-4051, Conen, David; https://orcid.org/0000-0002-2459-5251, and Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896

Abstract

BACKGROUND An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking. AIMS To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients. METHODS Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education. RESULTS Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The

Published
2023

35. Longitudinal Changes in Health-Related Quality of Life in Patients With Atrial Fibrillation

Author

Foster-Witassek, Fabienne; https://orcid.org/0000-0002-1631-5838, Aebersold, Helena; https://orcid.org/0000-0002-4418-9904, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Ammann, Peter, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Blozik, Eva; https://orcid.org/0009-0004-6773-4487, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Cattaneo, Mattia, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Felder, Stefan; https://orcid.org/0000-0002-5029-7274, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Müller, Andreas; https://orcid.org/0000-0001-7845-9012, Netzer, Seraina, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Stauber, Annina; https://orcid.org/0009-0008-6006-8177, Sticherling, Christian; https://orcid.org/0000-0001-8428-7050, Szucs, Thomas; https://orcid.org/0000-0003-0195-3316, Conen, David; https://orcid.org/0000-0002-2459-5251, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Serra-Burriel, Miquel; https://orcid.org/0000-0001-8595-1224, Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173, Foster-Witassek, Fabienne; https://orcid.org/0000-0002-1631-5838, Aebersold, Helena; https://orcid.org/0000-0002-4418-9904, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Ammann, Peter, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Blozik, Eva; https://orcid.org/0009-0004-6773-4487, Bonati, Leo H; https://orcid.org/0000-0003-1163-8133, Cattaneo, Mattia, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Felder, Stefan; https://orcid.org/0000-0002-5029-7274, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Müller, Andreas; https://orcid.org/0000-0001-7845-9012, Netzer, Seraina, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Stauber, Annina; https://orcid.org/0009-0008-6006-8177, Sticherling, Christian; https://orcid.org/0000-0001-8428-7050, Szucs, Thomas; https://orcid.org/0000-0003-0195-3316, Conen, David; https://orcid.org/0000-0002-2459-5251, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Serra-Burriel, Miquel; https://orcid.org/0000-0001-8595-1224, and Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173

Abstract

Background: Optimizing health-related quality of life (HRQoL) is an important aim of atrial fibrillation (AF) treatment. Little is known about patients' long-term HRQoL trajectories and the impact of patient and disease characteristics. The aim of this study was to describe HRQoL trajectories in an observational AF study population and in clusters of patients with similar patient and disease characteristics. Methods and Results: We used 5-year follow-up data from the Swiss-Atrial Fibrillation prospective cohort, which enrolled 2415 patients with prevalent AF from 2014 to 2017. HRQoL data, collected yearly, comprised EuroQoL-5 dimension utilities and EuroQoL visual analog scale scores. Patient clusters with similar characteristics at enrollment were identified using hierarchical clustering. HRQoL trajectories were analyzed descriptively and with inverse probability-weighted regressions. Effects of postbaseline clinical events were additionally assessed using time-shifted event variables. Among 2412 (99.9%) patients with available baseline HRQoL, 3 clusters of patients with AF were identified, which we characterized as follows: "cardiovascular dominated," "isolated symptomatic," and "severely morbid without cardiovascular disease." Utilities and EuroQoL visual analog scale scores remained stable over time for the full population and the clusters; isolated symptomatic patients showed higher levels of HRQoL. Utilities were reduced after occurrences of stroke, hospitalization for heart failure, and bleeding, by -0.12 (95% CI, -0.18 to -0.06), -0.10 (95% CI, -0.13 to -0.08), and -0.06 (95% CI, -0.08 to -0.04), respectively, on a 0 to 1 utility scale. Utility of surviving patients returned to preevent levels 4 years after heart failure hospitalization; 3 years after bleeding; and 1 year after stroke. Conclusions: In patients with prevalent AF, HRQoL was stable over time, irrespective of baseline patient characteristics. Clinical events of hospitalization for heart failure

Published
2023

36. Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach

Author

Serra-Burriel, Miquel; https://orcid.org/0000-0001-8595-1224, Aebersold, Helena; https://orcid.org/0000-0002-4418-9904, Foster-Witassek, Fabienne; https://orcid.org/0000-0002-1631-5838, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Blum, Manuel R, Sticherling, Christian; https://orcid.org/0000-0001-8428-7050, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Krisai, Philipp; https://orcid.org/0000-0002-4367-2363, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Conen, David; https://orcid.org/0000-0002-2459-5251, Felder, Stefan; https://orcid.org/0000-0002-5029-7274, Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173, Serra-Burriel, Miquel; https://orcid.org/0000-0001-8595-1224, Aebersold, Helena; https://orcid.org/0000-0002-4418-9904, Foster-Witassek, Fabienne; https://orcid.org/0000-0002-1631-5838, Coslovsky, Michael; https://orcid.org/0000-0001-7678-7354, Rodondi, Nicolas; https://orcid.org/0000-0001-9083-6896, Blum, Manuel R, Sticherling, Christian; https://orcid.org/0000-0001-8428-7050, Moschovitis, Giorgio; https://orcid.org/0000-0002-4043-8061, Beer, Jürg H; https://orcid.org/0000-0002-7199-0406, Reichlin, Tobias; https://orcid.org/0000-0002-7197-8415, Krisai, Philipp; https://orcid.org/0000-0002-4367-2363, Aeschbacher, Stefanie; https://orcid.org/0000-0001-8134-2421, Paladini, Rebecca E; https://orcid.org/0000-0002-4502-1978, Kühne, Michael; https://orcid.org/0000-0002-2937-3711, Osswald, Stefan; https://orcid.org/0000-0002-9240-6731, Conen, David; https://orcid.org/0000-0002-2459-5251, Felder, Stefan; https://orcid.org/0000-0002-5029-7274, and Schwenkglenks, Matthias; https://orcid.org/0000-0001-7217-1173

Abstract

OBJECTIVES Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings.

Published
2023

37. Longitudinal Changes in Health-Related Quality of Life in Patients With Atrial Fibrillation.

Author

Foster-Witassek, Fabienne, Aebersold, Helena, Aeschbacher, Stefanie, Ammann, Peter, Beer, Jürg H., Blozik, Eva, Bonati, Leo H., Cattaneo, Mattia, Coslovsky, Michael, Felder, Stefan, Moschovitis, Giorgio, Müller, Andreas, Netzer, Seraina, Paladini, Rebecca E., Reichlin, Tobias, Rodondi, Nicolas, Stauber, Annina, Sticherling, Christian, Szucs, Thomas, and Conen, David

Published
2023
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39. Deleterious role of endothelial lectin-like oxidized low-density lipoprotein receptor-1 in ischaemia/reperfusion cerebral injury

Author

Akhmedov, Alexander, Bonetti, Nicole R, Reiner, Martin F, Spescha, Remo D, Amstalden, Heidi, Merlini, Mario, Gaul, Daniel S, Diaz-Cañestro, Candela, Briand-Schumacher, Sylvie, Spescha, Rebecca S, Semerano, Aurora, Giacalone, Giacomo, Savarese, Gianluigi, Montecucco, Fabrizio, Kulic, Luka, Nitsch, Roger M, Matter, Christian M, Kullak-Ublick, Gerd A, Sessa, Maria, Lüscher, Thomas F, Beer, Jürg H, Liberale, Luca, and Camici, Giovanni G

Published
2019
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40. Bone Morphogenetic Protein 10-A Novel Biomarker to Predict Adverse Outcomes in Patients With Atrial Fibrillation

Author

Hennings, Elisa, Blum, Steffen, Aeschbacher, Stefanie, Coslovsky, Michael, Knecht, Sven, Eken, Ceylan, Lischer, Mirko, Paladini, Rebecca E, Krisai, Philipp, Reichlin, Tobias, Rodondi, Nicolas, Beer, Jürg H, Ammann, Peter, Conte, Giulio, De Perna, Maria Luisa, Kobza, Richard, Blum, Manuel R, Bossard, Matthias, Kastner, Peter, Ziegler, André, Müller, Christian, Bonati, Leo H, Pfister, Otmar, Zuern, Christine S, Conen, David, Kühne, Michael, and Osswald, Stefan

Subjects
360 Social problems & social services, 610 Medicine & health, Cardiology and Cardiovascular Medicine
Abstract

Background Patients with atrial fibrillation (AF) face an increased risk of death and major adverse cardiovascular events (MACE). We aimed to assess the predictive value of the novel atrial‐specific biomarker BMP10 (bone morphogenetic protein 10) for death and MACE in patients with AF in comparison with NT‐proBNP (N‐terminal prohormone of B‐type natriuretic peptide). Methods and Results BMP10 and NT‐proBNP were measured in patients with AF enrolled in Swiss‐AF (Swiss Atrial Fibrillation Study), a prospective multicenter cohort study. A total of 2219 patients were included (median follow‐up 4.3 years [interquartile range 3.9, 5.1], mean age 73±9 years, 73% male). In multivariable Cox proportional hazard models, the adjusted hazard ratio (aHR) associated with 1 ng/mL increase of BMP10 was 1.60 (95% CI, 1.37–1.87) for all‐cause death, and 1.54 (95% CI, 1.35–1.76) for MACE. For all‐cause death, the concordance index was 0.783 (95% CI, 0.763–0.809) for BMP10, 0.784 (95% CI, 0.765–0.810) for NT‐proBNP, and 0.789 (95% CI, 0.771–0.815) for both biomarkers combined. For MACE, the concordance index was 0.732 (95% CI, 0.715–0.754) for BMP10, 0.747 (95% CI, 0.731–0.768) for NT‐proBNP, and 0.750 (95% CI, 0.734–0.771) for both biomarkers combined. When grouping patients according to NT‐proBNP categories (900 ng/L), higher aHRs were observed in patients with high BMP10 in the categories of low NT‐proBNP (all‐cause death aHR, 2.28 [95% CI, 1.15–4.52], MACE aHR, 1.88 [95% CI, 1.07–3.28]) and high NT‐proBNP (all‐cause death aHR, 1.61 [95% CI, 1.14–2.26], MACE aHR, 1.38 [95% CI, 1.07–1.80]). Conclusions BMP10 strongly predicted all‐cause death and MACE in patients with AF. BMP10 provided additional prognostic information in low‐ and high‐risk patients according to NT‐proBNP stratification. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02105844.

Published
2023

41. Association of Statin Use and Lipid Levels with Cerebral Microbleeds and Intracranial Hemorrhage in Patients with Atrial Fibrillation: a Prospective Cohort Study

Author

Moutzouri, Elisavet, Glutz, Matthias, Abolhassani, Nazanin, Feller, Martin, Adam, Luise, Gencer, Baris, Del Giovane, Cinzia, Bétrisey, Sylvain, Paladini, Rebecca E, Hennings, Elisa, Aeschbacher, Stefanie, Beer, Jürg H, Moschovitis, Giorgio, Seiffge, David J, De Marchis, Gian Marco, Coslovsky, Michael, Reichlin, Tobias, Conte, Giulio, Sinnecker, Tim, Schwenkglenks, Matthias, Bonati, Leo H, Kastner, Peter, Aujesky, Drahomir Antonin, Kühne, Michael, Osswald, Stefan, Fischer, Urs, Conen, David, and Rodondi, Nicolas

Subjects
Neurology, 360 Social problems & social services, 610 Medicine & health
Abstract

Background: An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported; but data on the relationship between statin-use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk are lacking. Aims: To explore the association between statin-use and blood lipid-levels with the prevalence and progression of CMBs in patients with atrial fibrillation with particular focus on anticoagulated patients. Methods: Data of Swiss-AF, a prospective cohort of patients with established AF were analyzed. Statin-use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2-years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin-use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2-years compared to baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use and education. Results: Of the 1693 patients with CMB data at baseline MRI (mean±SD age 72.5±8.4y, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI, 0.83–1.45). AdjOR for 1 unit increase in LDL-levels was 0.95 (95% CI, 0.82–1.10). At 2-years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI, 0.66–1.80). There was no association between LDL-levels and CMBs progression (adjOR 1.02, 95% CI, 0.79–1.32). At follow-up 14 (1.2%) statin users had ICH vs 16 (1.3%) non-users. The age and sex adjusted Hazard Ratio (adjHR) was 0.75 (95% CI, 0.36–1.55). Results remained robust in sensitivity analyses excluding participants without anticoagulants. Conclusions: In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.

Published
2023
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42. JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study

Author

Liberale, Luca, Puspitasari, Yustina M, Ministrini, Stefano, Akhmedov, Alexander, Kraler, Simon, Bonetti, Nicole R, Beer, Georgia, Vukolic, Ana, Bongiovanni, Dario, Han, Jiaying, Kirmes, Kilian, Bernlochner, Isabell, Pelisek, Jaroslav, Beer, Jürg H, Jin, Zheng-Gen, Pedicino, Daniela, Liuzzo, Giovanna, Stellos, Konstantinos, Montecucco, Fabrizio, Crea, Filippo, Lüscher, Thomas F, Camici, Giovanni G, and University of Zurich

Subjects
11548 Clinic for Vascular Surgery, 610 Medicine & health, Cardiology and Cardiovascular Medicine
Abstract

Aims Variants of the junctional cadherin 5 associated (JCAD) locus associate with acute coronary syndromes. JCAD promotes experimental atherosclerosis through the large tumor suppressor kinase 2 (LATS2)/Hippo pathway. This study investigates the role of JCAD in arterial thrombosis. Methods and results JCAD knockout (Jcad−/−) mice underwent photochemically induced endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) treated with JCAD small interfering RNA (siJCAD), LATS2 small interfering RNA (siLATS2) or control siRNA (siSCR) were employed for in vitro assays. Plasma JCAD was measured in patients with chronic coronary syndrome or ST-elevation myocardial infarction (STEMI). Jcad−/− mice displayed reduced thrombogenicity as reflected by delayed time to carotid occlusion. Mechanisms include reduced activation of the coagulation cascade [reduced tissue factor (TF) expression and activity] and increased fibrinolysis [higher thrombus embolization episodes and D-dimer levels, reduced vascular plasminogen activator inhibitor (PAI)-1 expression]. In vitro, JCAD silencing inhibited TF and PAI-1 expression in HAECs. JCAD-silenced HAECs (siJCAD) displayed increased levels of LATS2 kinase. Yet, double JCAD and LATS2 silencing did not restore the control phenotype. si-JCAD HAECs showed increased levels of phosphoinositide 3-kinases (PI3K)/ proteinkinase B (Akt) activation, known to downregulate procoagulant expression. The PI3K/Akt pathway inhibitor—wortmannin—prevented the effect of JCAD silencing on TF and PAI-1, indicating a causative role. Also, co-immunoprecipitation unveiled a direct interaction between JCAD and Akt. Confirming in vitro findings, PI3K/Akt and P-yes-associated protein levels were higher in Jcad−/− animals. Lastly, as compared with chronic coronary syndrome, STEMI patients showed higher plasma JCAD, which notably correlated positively with both TF and PAI-1 levels. Conclusions JCAD promotes arterial thrombosis by modulating coagulation and fibrinolysis. Herein, reported translational data suggest JCAD as a potential therapeutic target for atherothrombosis.

Published
2023
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43. sj-docx-1-wso-10.1177_17474930231181010 – Supplemental material for Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study

Author

Moutzouri, Elisavet, Glutz, Matthias, Abolhassani, Nazanin, Feller, Martin, Adam, Luise, Gencer, Baris, Del Giovane, Cinzia, Bétrisey, Sylvain, Paladini, Rebecca E, Hennings, Elisa, Aeschbacher, Stefanie, Beer, Jürg H, Moschovitis, Giorgio, Seiffge, David, De Marchis, Gian Marco, Coslovsky, Michael, Reichlin, Tobias, Conte, Giulio, Sinnecker, Tim, Schwenkglenks, Matthias, Bonati, Leo H, Kastner, Peter, Aujesky, Drahomir, Kühne, Michael, Osswald, Stefan, Fischer, Urs, Conen, David, and Rodondi, Nicolas

Subjects
FOS: Clinical medicine, Cardiology, Medicine, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, sj-docx-1-wso-10.1177_17474930231181010 for Association of statin use and lipid levels with cerebral microbleeds and intracranial hemorrhage in patients with atrial fibrillation: A prospective cohort study by Elisavet Moutzouri, Matthias Glutz, Nazanin Abolhassani, Martin Feller, Luise Adam, Baris Gencer, Cinzia Del Giovane, Sylvain Bétrisey, Rebecca E Paladini, Elisa Hennings, Stefanie Aeschbacher, Jürg H Beer, Giorgio Moschovitis, David Seiffge, Gian Marco De Marchis, Michael Coslovsky, Tobias Reichlin, Giulio Conte, Tim Sinnecker, Matthias Schwenkglenks, Leo H Bonati, Peter Kastner, Drahomir Aujesky, Michael Kühne, Stefan Osswald, Urs Fischer, David Conen and Nicolas Rodondi in International Journal of Stroke

Published
2023
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44. Omega-3 Fatty Acids and Heart Rhythm, Rate, and Variability in Atrial Fibrillation

Author

Baumgartner, Philipp, Reiner, Martin F, Wiencierz, Andrea, Coslovsky, Michael, Bonetti, Nicole R, Filipovic, Mark G, Aeschbacher, Stefanie, Kühne, Michael, Zuern, Christine S, Rodondi, Nicolas, Oberle, Jolanda, Moschovitis, Giorgio, Lüscher, Thomas F, Camici, Giovanni G, Osswald, Stefan, Conen, David, and Beer, Jürg H

Subjects
360 Social problems & social services, 610 Medicine & health
Abstract

Background Previous randomized control trials showed mixed results concerning the effect of omega-3 fatty acids (n-3 FAs) on atrial fibrillation (AF). The associations of n-3 FA blood levels with heart rhythm in patients with established AF are unknown. The goal of this study was to assess the associations of total and individual n-3 FA blood levels with AF type (paroxysmal versus nonparoxysmal), heart rate (HR), and HR variability in patients with AF. Methods and Results Total n-3 FAs, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, and alpha-linolenic acid blood levels were determined in 1969 patients with known AF from the SWISS-AF (Swiss Atrial Fibrillation cohort). Individual and total n-3 FAs were correlated with type of AF, HR, and HR variability using standard logistic and linear regression, adjusted for potential confounders. Only a mild association with nonparoxysmal AF was found with total n-3 FA (odds ratio [OR], 0.97 [95% CI, 0.89-1.05]) and docosahexaenoic acid (OR, 0.93 [95% CI, 0.82-1.06]), whereas other individual n-3 FAs showed no association with nonparoxysmal AF. Higher total n-3 FAs (estimate 0.99 [95% CI, 0.98-1.00]) and higher docosahexaenoic acid (0.99 [95% CI, 0.97-1.00]) tended to be associated with slower HR in multivariate analysis. Docosapentaenoic acid was associated with a lower HR variability triangular index (0.94 [95% CI, 0.89-0.99]). Conclusions We found no strong evidence for an association of n-3 FA blood levels with AF type, but higher total n-3 FA levels and docosahexaenoic acid might correlate with lower HR, and docosapentaenoic acid with a lower HR variability triangular index.

Published
2023
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46. JCAD promotes arterial thrombosis through PI3K/Akt modulation: a translational study

Author

Liberale, Luca, primary, Puspitasari, Yustina M, additional, Ministrini, Stefano, additional, Akhmedov, Alexander, additional, Kraler, Simon, additional, Bonetti, Nicole R, additional, Beer, Georgia, additional, Vukolic, Ana, additional, Bongiovanni, Dario, additional, Han, Jiaying, additional, Kirmes, Kilian, additional, Bernlochner, Isabell, additional, Pelisek, Jaroslav, additional, Beer, Jürg H, additional, Jin, Zheng-Gen, additional, Pedicino, Daniela, additional, Liuzzo, Giovanna, additional, Stellos, Konstantinos, additional, Montecucco, Fabrizio, additional, Crea, Filippo, additional, Lüscher, Thomas F, additional, and Camici, Giovanni G, additional

Published
2022
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47. Differences in duration of anticoagulation after pulmonary embolism and deep vein thrombosis: Findings from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

Author

Wenger, Nicolas, primary, Sebastian, Tim, additional, Beer, Jürg H., additional, Mazzolai, Lucia, additional, Aujesky, Drahomir, additional, Hayoz, Daniel, additional, Engelberger, Rolf P., additional, Korte, Wolfgang, additional, Voci, Davide, additional, Kucher, Nils, additional, Barco, Stefano, additional, and Spirk, David, additional

Published
2022
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48. Neurocognitive function in patients with atrial fibrillation undergoing pulmonary vein isolation

Author

Zwimpfer, Leon, primary, Aeschbacher, Stefanie, additional, Krisai, Philipp, additional, Coslovsky, Michael, additional, Springer, Anne, additional, Paladini, Rebecca E., additional, Girod, Marc, additional, Hufschmid, Janik, additional, Knecht, Sven, additional, Badertscher, Patrick, additional, Beer, Jürg H., additional, Bonati, Leo H., additional, Zuern, Christine S., additional, Roten, Laurent, additional, Reichlin, Tobias, additional, Sticherling, Christian, additional, Conen, David, additional, Osswald, Stefan, additional, and Kühne, Michael, additional

Published
2022
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49. Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing

Author

Meyre, Pascal B, primary, Blum, Steffen, additional, Hennings, Elisa, additional, Aeschbacher, Stefanie, additional, Reichlin, Tobias, additional, Rodondi, Nicolas, additional, Beer, Jürg H, additional, Stauber, Annina, additional, Müller, Andreas, additional, Sinnecker, Tim, additional, Moutzouri, Elisavet, additional, Paladini, Rebecca E, additional, Moschovitis, Giorgio, additional, Conte, Giulio, additional, Auricchio, Angelo, additional, Ramadani, Alexandra, additional, Schwenkglenks, Matthias, additional, Bonati, Leo H, additional, Kühne, Michael, additional, Osswald, Stefan, additional, and Conen, David, additional

Published
2022
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50. SGLT-2 inhibition by empagliflozin has no effect on experimental arterial thrombosis in a murine model of low-grade inflammation

Author

Liberale, Luca, primary, Kraler, Simon, additional, Puspitasari, Yustina M, additional, Bonetti, Nicole R, additional, Akhmedov, Alexander, additional, Ministrini, Stefano, additional, Montecucco, Fabrizio, additional, Marx, Nikolaus, additional, Lehrke, Michael, additional, Hartmann, Niels Ulrik K, additional, Beer, Jürg H, additional, Wenzl, Florian A, additional, Paneni, Francesco, additional, Lüscher, Thomas F, additional, and Camici, Giovanni G, additional

Published
2022
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