Kimon Stamatelopoulos1, Dirk Sibbing2, Loukianos S Rallidis3, Georgios Georgiopoulos1, Dimitrios Stakos4, Siegmund Braun5, Aikaterini Gatsiou6, Kateryna Sopova7, Christos Kotakos3, Christos Varounis3, Constantinos C Tellis8, Efstathios Kastritis1, Maria Alevizaki1, Alexandros D Tselepis8, Panagiotis Alexopoulos9, Christoph Laske10, Till Keller11, Adnan Kastrati12, Stefanie Dimmeler13, Andreas M Zeiher11, Konstantinos Stellos14. 1. Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece. 2. Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. 3. Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece. 4. Cardiology Clinic, Democritus University of Thrace, Alexandroupolis, Greece. 5. Deutsches Herzzentrum, Technische Universität, Munich, Germany. 6. Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany. 7. Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany. 8. Atherothrombosis Research Center/Department of Chemistry, University of Ioannina, Ioannina, Greece. 9. Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. 10. Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany; Section for Dementia Research, Hertie-Institute of Clinical Brain Research, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany. 11. Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany. 12. Deutsches Herzzentrum, Technische Universität, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. 13. Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany. 14. Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany. Electronic address: konstantinos.stellos@kgu.de.
Abstract
BACKGROUND: The amyloid beta peptide is the major protein constituent of neuritic plaques in Alzheimer disease and appears to play a central role in vascular inflammation pathophysiology. OBJECTIVES: This study sought to determine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. METHODS: Abeta40 was retrospectively measured in blood samples collected from 3 independent prospective cohorts and 2 case-control cohorts (total N = 1,464). Major adverse cardiac events (MACE) were assessed in the 2 prospective cohorts (n = 877) followed for a median of 4.4 years. To look at effects on subclinical disease, arterial stiffness was evaluated at baseline and after 5-year follow-up (n = 107) in young healthy subjects. The primary endpoint was the predictive value of Abeta40 for CV mortality and outcomes in patients with CHD. RESULTS: In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein, and high-sensitivity troponin T, Abeta40 independently predicted CV death and MACE in patients with CHD (p < 0.05 for all). After multivariate adjustment, Abeta40 levels conferred a substantial enhancement of net reclassification index and integrated discrimination improvement of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Abeta40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis, and incident CHD. CONCLUSIONS: Measuring blood levels of Abeta40 identified patients at high risk for CV death.
BACKGROUND: The amyloid beta peptide is the major protein constituent of neuritic plaques in Alzheimer disease and appears to play a central role in vascular inflammation pathophysiology. OBJECTIVES: This study sought to determine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects. METHODS: Abeta40 was retrospectively measured in blood samples collected from 3 independent prospective cohorts and 2 case-control cohorts (total N = 1,464). Major adverse cardiac events (MACE) were assessed in the 2 prospective cohorts (n = 877) followed for a median of 4.4 years. To look at effects on subclinical disease, arterial stiffness was evaluated at baseline and after 5-year follow-up (n = 107) in young healthy subjects. The primary endpoint was the predictive value of Abeta40 for CV mortality and outcomes in patients with CHD. RESULTS: In Cox proportional hazards models adjusted for age, sex, estimated glomerular filtration rate, left ventricular ejection fraction, high-sensitivity C-reactive protein, and high-sensitivity troponin T, Abeta40 independently predicted CV death and MACE in patients with CHD (p < 0.05 for all). After multivariate adjustment, Abeta40 levels conferred a substantial enhancement of net reclassification index and integrated discrimination improvement of individuals at risk in the total combined CHD cohort over the best predictive model. Further cohort-based analysis revealed that Abeta40 levels were significantly and independently associated with arterial stiffness progression, incident subclinical atherosclerosis, and incident CHD. CONCLUSIONS: Measuring blood levels of Abeta40 identified patients at high risk for CV death.
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