Kimon Stamatelopoulos, MD *; Matthias Mueller-Hennessen, MD *; Georgios Georgiopoulos, MD *; Marco Sachse; Jasper Boeddinghaus, MD; Kateryna Sopova, MD; Aikaterini Gatsiou, MSc; Carolin Amrhein; Moritz Biener, MD; Mehrshad Vafaie, MD; Fani Athanasouli, MD; Dimitrios Stakos, MD; Konstantinos Pateras, MSc; Raphael Twerenbold, MD; Patrick Badertscher, MD; Thomas Nestelberger, MD; Stefanie Dimmeler, PhD; Hugo A. Katus, MD; Andreas M. Zeiher, MD; Christian Mueller, MD; Evangelos Giannitsis, MD *; Konstantinos Stellos, MD *
Acknowledgment: The authors thank Jose Coelho Lima Jr. and Nikolaos Vlachogiannis for proofreading the manuscript.
Grant Support: By an Inge-Edler Research Scholarship from the German Cardiac Society.
Disclosures: The authors declare that none have a relationship with pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject of the article. Dr. Mueller-Hennessen reports grants from Heidelberg University Faculty of Medicine during the conduct of the study and grants and nonfinancial support from BRAHMS Thermo Scientific; nonfinancial support from Bayer Vital, Metanomics Health, and Philips Electronics; and grants and personal fees from Roche Diagnostics outside the submitted work. Dr. Biener reports grants and nonfinancial support from AstraZeneca, nonfinancial support from Thermo Fisher, and grants from Roche outside the submitted work. Dr. Vafaie reports financial support for clinical trials from Bayer Healthcare Germany and Daiichi Sankyo and has been reimbursed for travel expenses and fees associated with attending seminars and conferences by Bayer Vital, Daiichi Sankyo, Teva, Octapharma, Lilly Germany, GlaxoSmithKline, Roche Diagnostics, BRAHMS, Leo Pharma, and Abbott. Dr. Twerenbold reports grants from the Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, and University Hospital of Basel and personal fees from Roche, Abbott, Siemens, Singulex, and BRAHMS Thermo Scientific outside the submitted work. Dr. Katus reports personal fees from Bayer Vital, Daiichi Sankyo, and Roche Diagnostics outside the submitted work. Dr. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the Stiftung für kardiovaskuläre Forschung Basel, Abbott, Alere, AstraZeneca, Beckman Coulter, Biomerieux, Brahms, Roche, Siemens, Singulex, Sphingotec, and the Department of Internal Medicine at University Hospital Basel, as well as speaker or consulting honoraria from Abbott, Alere, AstraZeneca, Biomerieux, Boehringer Ingelheim, BMS, Brahms, Cardiorentis, Novartis, Roche, Siemens, and Singulex. Dr. Giannitsis reports personal fees from Bayer Vital, AstraZeneca, Daiichi Sankyo, and Roche Diagnostics outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1540.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Available on request for reviewing purposes only (e-mail, firstname.lastname@example.org). Statistical code: Available on request (e-mail, email@example.com).
Corresponding Author: Konstantinos Stellos, MD, Cardiovascular Research Centre, Institute of Genetic Medicine, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Stamatelopoulos, Georgiopoulos, and Athanasouli: Vascular Laboratory, Department of Clinical Therapeutics, Alexandra Hospital, 80 Vasilissis Sofias, PO Box 11528, Athens, Greece.
Drs. Mueller-Hennessen, Biener, Vafaie, Katus, and Giannitsis: Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Mr. Sachse, Ms. Gatsiou, Ms. Amrhein, and Dr. Dimmeler: Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Drs. Boeddinghaus, Twerenbold, Badertscher, Nestelberger, and Mueller: Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital Basel, University of Basel, Spitalstrasse 2, CH-4056 Basel, Switzerland.
Drs. Sopova and Zeiher: Department of Cardiology, Goethe University Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Dr. Stakos: Department of Cardiology, Democritus University of Thrace, Dragana, Alexandroupolis 68100, Greece.
Mr. Pateras: Department of Biostatistics and Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Huispost nr. STR 6.131, PO Box 85500, 3508 GA Utrecht, the Netherlands.
Dr. Stellos: Cardiovascular Research Centre, Institute of Genetic Medicine, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom.
Author Contributions: Conception and design: K. Stamatelopoulos, K. Stellos.
Analysis and interpretation of the data: K. Stamatelopoulos, M. Mueller-Hennessen, G. Georgiopoulos, J. Boeddinghaus, K. Sopova, A. Gatsiou, D. Stakos, K. Pateras, P. Badertscher, T. Nestelberger, H.A. Katus, A.M. Zeiher, C. Mueller, E. Giannitsis, K. Stellos.
Drafting of the article: K. Stamatelopoulos, G. Georgiopoulos, K. Stellos.
Critical revision of the article for important intellectual content: K. Stamatelopoulos, M. Mueller-Hennessen, G. Georgiopoulos, J. Boeddinghaus, K. Sopova, A. Gatsiou, M. Biener, M. Vafaie, D. Stakos, K. Pateras, R. Twerenbold, P. Badertscher, T. Nestelberger, H.A. Katus, S. Dimmeler, A.M. Zeiher, E. Giannitsis, K. Stellos.
Final approval of the article: K. Stamatelopoulos, M. Mueller-Hennessen, G. Georgiopoulos, M. Sachse, J. Boeddinghaus, K. Sopova, A. Gatsiou, C. Amrhein, M. Biener, M. Vafaie, F. Athanasouli, D. Stakos, K. Pateras, R. Twerenbold, P. Badertscher, T. Nestelberger, S. Dimmeler, H.A. Katus, A.M. Zeiher, C. Mueller, E. Giannitsis, K. Stellos.
Provision of study materials or patients: M. Mueller-Hennessen, J. Boeddinghaus, P. Badertscher, H.A. Katus, C. Mueller, E. Giannitsis.
Statistical expertise: M. Mueller-Hennessen, G. Georgiopoulos, J. Boeddinghaus, K. Pateras, R. Twerenbold, E. Giannitsis, K. Stellos.
Obtaining of funding: S. Dimmeler, C. Mueller, K. Stellos.
Administrative, technical, or logistic support: M. Mueller-Hennessen, M. Sachse, A. Gatsiou, C. Amrhein, C. Mueller, K. Stellos.
Collection and assembly of data: M. Mueller-Hennessen, M. Sachse, J. Boeddinghaus, A. Gatsiou, C. Amrhein, R. Twerenbold, P. Badertscher, T. Nestelberger, C. Mueller, E. Giannitsis, K. Stellos.
Amyloid-β (1-40) (Aβ40) is implicated in mechanisms related to plaque destabilization and correlates with adverse outcomes in stable coronary artery disease.
To determine the prognostic and reclassification value of baseline circulating levels of Aβ40 after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is widely recommended for risk stratification in non–ST-segment elevation acute coronary syndrome (NSTE-ACS).
Retrospective cohort study using data from 2 independent prospective cohorts, the Heidelberg study (n = 1145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation) study (n = 734).
Academic hospitals in 7 European countries.
Patients with adjudicated NSTE-ACS followed for a median of 21.9 and 24.9 months in the Heidelberg and APACE studies, respectively.
All-cause mortality was the primary end point.
Amyloid-β (1-40) was associated with mortality after multivariate adjustment for age, sex, diabetes mellitus, high-sensitivity cardiac troponin T and C-reactive protein, revascularization, and ACS type (Heidelberg cohort hazard ratio [HR] for 80th vs. 20th percentiles, 1.66 [95% CI, 1.06 to 2.61; P = 0.026]; APACE cohort HR, 1.50 [CI, 1.15 to 1.96; P = 0.003]). It was also associated with mortality after adjustment for the GRACE score (Heidelberg cohort HR for 80th vs. 20th percentiles, 1.11 [CI, 1.04 to 1.18; P = 0.001]; APACE cohort HR, 1.39 [CI, 1.02 to 1.88; P = 0.036]). Amyloid-β (1-40) correctly reclassified risk for death over the GRACE score (net reclassification index, 33.4% and 47.1% for the Heidelberg and APACE cohorts, respectively) (P < 0.05).
At low concentrations of Aβ40, dose–response associations with mortality differed between cohorts, possibly because of varying blood preparations used to measure Aβ40.
Circulating Aβ40 is a predictor of mortality and improves risk stratification of patients with NSTE-ACS over the GRACE score recommended by clinical guidelines. The clinical application of Aβ40 as a novel biomarker in NSTE-ACS should be further explored and validated.
German Cardiac Society.
Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Sachse M, Boeddinghaus J, Sopova K, et al. Amyloid-β (1-40) and Mortality in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study. Ann Intern Med. ;168:855–865. doi: 10.7326/M17-1540
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Published: Ann Intern Med. 2018;168(12):855-865.
Published at www.annals.org on 22 May 2018
Acute Coronary Syndromes, Cardiac Diagnosis and Imaging, Cardiology, Coronary Heart Disease, Emergency Medicine.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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