Roland Klingenberg1,2,3, Soheila Aghlmandi4,5,6, Christoph Liebetrau2,3, Lorenz Räber7, Baris Gencer8, David Nanchen9, David Carballo8, Alexander Akhmedov1, Fabrizio Montecucco8,10, Stefan Zoller11, Chad Brokopp12, Dik Heg4,5, Peter Jüni13, Helena Marti Soler14, Pedro-Manuel Marques-Vidal14, Peter Vollenweider14, Oliver Dörr15, Nicolas Rodondi16,17, François Mach8, Stephan Windecker7, Ulf Landmesser1,18, Arnold von Eckardstein19, Christian W Hamm2,3,15, Christian M Matter1, Thomas F Lüscher1. 1. Department of Cardiology, University Heart Center, University Hospital of Zurich and Center for Molecular Cardiology, University of Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland and Wagistr. 12, CH-8952 Schlieren, Switzerland. 2. Department of Cardiology, Kerckhoff Heart and Thorax Center, Kerckhoff-Klinik, Benekestr. 2-8, D-61231 Bad Nauheim, Germany. 3. DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Benekestr. 2-8, D-61231 Bad Nauheim, Germany. 4. Institute of Social and Preventive Medicine (ISPM), University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland. 5. CTU Bern, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland. 6. Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Spitalstr. 12, CH-4056 Basel, Switzerland. 7. Department of Cardiology, Cardiovascular Center, University Hospital of Bern, Freiburgstr. 18, CH-3010 Bern, Switzerland. 8. Department of Cardiology, Cardiovascular Center, University Hospital of Geneva, Rue Gabrielle-Perret-Gentil 4, CH-1211 Geneva 14, Switzerland. 9. Department of Ambulatory Care and Community Medicine, University of Lausanne, Rue du Bugnon 44, CH-1011 Lausanne, Switzerland. 10. First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6, Viale Benedetto XV, IT-16132 Genoa, Italy. 11. Bioinformatics, Genetic Diversity Center, Federal Institute of Technology (ETH), Universitätsstr. 16, CH-8092 Zurich, Switzerland. 12. Department of Cardiothoracic Surgery, Regenerative Medicine Center, Department of Cardiothoracic Surgery, University Hospital of Zurich, Wagistr. 12, CH-8952 Schlieren, Switzerland. 13. Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, 209 Victoria St, Toronto, ON M5B 1T8, Canada. 14. Department of General Internal Medicine, University Hospital of Lausanne, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. 15. Department of Cardiology, University Hospital of Giessen, Klinikstr. 33; D-35392 Giessen, Germany. 16. Institute of Primary Health Care (BIHAM), University of Bern, Gesellschaftsstr. 49, CH-3012 Bern, Switzerland. 17. Department of General Internal Medicine, University Hospital of Bern, Freiburgstr. 18, CH-3010 Bern, Switzerland. 18. Department of Cardiology, Charité Campus Benjamin-Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. 19. Institute of Clinical Chemistry, University Hospital of Zurich, Rämistr. 100, CH-8091 Zurich, Switzerland.
Abstract
AIMS: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. METHODS AND RESULTS: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. CONCLUSION: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. METHODS AND RESULTS: Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P < 0.001) comparable to high-sensitivity troponin T (30 days: 0.88 to 0.89, P < 0.001; 1 year: 0.77 to 0.79, P < 0.001). Similar results were obtained for the composite endpoint of all-cause mortality or myocardial infarction. Conversely, in a population-based case-control cohort (n = 362), Cyr61 was not associated with adverse outcome. CONCLUSION: Cyr61 is a novel early biomarker reflecting myocardial injury that improves risk stratification in ACS patients. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Sebastian Weichwald; Alessandro Candreva; Rebekka Burkholz; Roland Klingenberg; Lorenz Räber; Dik Heg; Robert Manka; Baris Gencer; François Mach; David Nanchen; Nicolas Rodondi; Stephan Windecker; Reijo Laaksonen; Stanley L Hazen; Arnold von Eckardstein; Frank Ruschitzka; Thomas F Lüscher; Joachim M Buhmann; Christian M Matter Journal: Eur Heart J Acute Cardiovasc Care Date: 2021-10-27
Authors: Nicolas Vuilleumier; Sabrina Pagano; Christophe Combescure; Baris Gencer; Julien Virzi; Lorenz Räber; David Carballo; Sebastian Carballo; David Nanchen; Nicolas Rodondi; Stephan Windecker; Stanley L Hazen; Zeneng Wang; Xinmin S Li; Arnold von Eckardstein; Christian M Matter; Thomas F Lüscher; Roland Klingenberg; Francois Mach Journal: J Clin Med Date: 2019-07-09 Impact factor: 4.241
Authors: Roland Klingenberg; Soheila Aghlmandi; Lorenz Räber; Alexander Akhmedov; Baris Gencer; David Carballo; David Nanchen; Heiner C Bucher; Nicolas Rodondi; François Mach; Stephan Windecker; Ulf Landmesser; Arnold von Eckardstein; Christian W Hamm; Thomas F Lüscher; Christian M Matter Journal: J Am Heart Assoc Date: 2021-10-08 Impact factor: 5.501
Authors: Patric Winzap; Allan Davies; Roland Klingenberg; Slayman Obeid; Marco Roffi; François Mach; Lorenz Räber; Stephan Windecker; Christian Templin; Fabian Nietlispach; David Nanchen; Baris Gencer; Olivier Muller; Christian M Matter; Arnold von Eckardstein; Thomas F Lüscher Journal: Cardiovasc Diabetol Date: 2019-10-31 Impact factor: 9.951