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

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  • Kimon Stamatelopoulos
  • Dirk Sibbing
  • Loukianos S Rallidis
  • Georgios Georgiopoulos
  • Dimitrios Stakos
  • Siegmund Braun
  • Kateryna Sopova
  • Christos Kotakos
  • Christos Varounis
  • Constantinos C Tellis
  • Efstathios Kastritis
  • Maria Alevizaki
  • Alexandros D Tselepis
  • Panagiotis Alexopoulos
  • Christoph Laske
  • Till Keller
  • Adnan Kastrati
  • Stefanie Dimmeler
  • Andreas M Zeiher
  • Konstantinos Stellos
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<mark>Journal publication date</mark>10/03/2015
<mark>Journal</mark>Journal of the American College of Cardiology
Issue number9
Volume65
Number of pages13
Pages (from-to)904-916
Publication StatusPublished
<mark>Original language</mark>English

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.

Bibliographic note

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.