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1. 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

2. IL-1 Antagonism in Men With Metabolic Syndrome and Low Testosterone: A Randomized Clinical Trial

Author

Philipp Schuetz, Simone Doerpfeld, Mirjam Christ-Crain, Fahim Ebrahimi, Sandrine Andrea Urwyler, Sven Straumann, Peter Neyer, Marc Y. Donath, Beat Mueller, and Luca Bernasconi

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Anti-Inflammatory Agents, Context (language use), 030204 cardiovascular system & hematology, Placebo, Biochemistry, 03 medical and health sciences, Grip strength, 0302 clinical medicine, Endocrinology, Double-Blind Method, Internal medicine, medicine, Humans, Testosterone, 030212 general & internal medicine, Obesity, Metabolic Syndrome, Anakinra, business.industry, Hypogonadism, Biochemistry (medical), Testosterone (patch), Middle Aged, medicine.disease, Interleukin 1 Receptor Antagonist Protein, Blood pressure, Treatment Outcome, Metabolic syndrome, business, Body mass index, medicine.drug, Interleukin-1
Abstract

Context Hypogonadism is highly prevalent among obese men with metabolic syndrome. Chronic low-grade inflammation is suspected to be a major cause for low testosterone levels in obese individuals. Objectives To test the inflammatory hypothesis of testosterone deficiency in metabolic syndrome. Design, setting, participants, and intervention In this randomized, placebo-controlled, double-blind trial involving men with metabolic syndrome, we randomly assigned 33 patients to receive 100 mg of anakinra (recombinant human IL-1 receptor antagonist) subcutaneously twice daily for 4 weeks and 34 patients to receive placebo. Main outcome measures The primary endpoint was the change from baseline in total testosterone levels after 4 weeks. Results The mean age was 54 years and baseline total testosterone levels were 9.3 nmol/L (95% CI, 8.7 to 10.0). At 4 weeks, total testosterone levels increased by 1.2 nmol/L (95% CI, 0.3 to 2.0; P = 0.01) in the anakinra group as compared with no change in the placebo group (0.01 nmol/L; 95% CI, -0.5 to 0.5; P = 0.99), resulting in a between-group difference of 0.96 nmol/L (95% CI, 0.3 to 1.9; P = 0.04). The effects were most pronounced with baseline C-reactive protein >2 mg/L (between-group difference 2.14 nmol/L; 95% CI, 0.11 to 4.17; P = 0.04) and body mass index >40 kg/m2 (between-group difference 2.64 nmol/L; 95% CI, 0.19 to 5.09; P = 0.04). Anakinra treatment did not exert benefits on fatigue and sexual dysfunction, but it improved grip strength of nondominant hand by 3.5 kg (95% CI 0.23 to 6.81; P = 0.04) and reduced mean arterial blood pressure by 2.9 mm Hg (95% CI, -5.99 to 0.19; P = 0.07). Conclusions Anti-inflammatory treatment with an antagonist of IL-1 led to an increase in testosterone levels in obese men with testosterone deficiency.

Published
2018

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