Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease.
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.


OBJECTIVE
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.
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
Kimon
K
Stamatelopoulos
Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität München, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Dirk
D
Sibbing
Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.
Loukianos S
LS
Rallidis
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
Georgios
G
Georgiopoulos
Cardiology Clinic, Democritus University of Thrace, Alexandroupolis, Greece.
Dimitrios
D
Stakos
Deutsches Herzzentrum, Technische Universität, Munich, Germany.
Siegmund
S
Braun
Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany.
Aikaterini
A
Gatsiou
Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany.
Kateryna
K
Sopova
Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.
Christos
C
Kotakos
Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.
Christos
C
Varounis
Atherothrombosis Research Center/Department of Chemistry, University of Ioannina, Ioannina, Greece.
Constantinos C
CC
Tellis
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
Efstathios
E
Kastritis
Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, Athens, Greece.
Maria
M
Alevizaki
Atherothrombosis Research Center/Department of Chemistry, University of Ioannina, Ioannina, Greece.
Alexandros D
AD
Tselepis
Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany.
Panagiotis
P
Alexopoulos
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.
Christoph
C
Laske
Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany.
Till
T
Keller
Deutsches Herzzentrum, Technische Universität, Munich, Germany; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
Adnan
A
Kastrati
Institute of Cardiovascular Regeneration, Centre of Molecular Medicine, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany.
Stefanie
S
Dimmeler
Department of Cardiology, J.W. Goethe University Frankfurt, Frankfurt am Main, Germany; German Center of Cardiovascular Research, Frankfurt, Germany.
Andreas M
AM
Zeiher
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.
Konstantinos
K
Stellos
D000367:Age Factors; D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D059168:Carotid Intima-Media Thickness; D002423:Cause of Death; D003327:Coronary Disease / Q000097:blood* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood*; D058226:Plaque, Atherosclerotic; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013318:Stroke Volume; D020107:Troponin T / Q000097:blood; D059289:Vascular Stiffness
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C078592:amyloid beta-protein (1-40); D002097:C-Reactive Protein
arterial stiffness; biomarker; risk stratification; subclinical atherosclerosis