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PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function

Johan De Sutter UGent, Nico R van de Veire, Sofie Struyf, Jan Philippé UGent, MARC DE BUYZERE UGent and Jo Van Damme (2012) PLOS ONE. 7(2).
abstract
Background: Platelet-derived chemokines are implicated in several aspects of vascular biology. However, for the chemokine platelet factor 4 variant (PF-4var/CXCL4L1), released by platelets during thrombosis and with different properties as compared to PF-4/CXCL4, its role in heart disease is not yet studied. We evaluated the determinants and prognostic value of the platelet-derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary artery disease (CAD). Methodology/Principal Findings: From 205 consecutive patients with stable CAD and preserved left ventricular (LV) function, blood samples were taken at inclusion and were analyzed for PF-4var, RANTES, platelet factor-4 and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Patients were followed (median follow-up 2.5 years) for the combined endpoint of cardiac death, non-fatal acute myocardial infarction, stroke or hospitalization for heart failure. Independent determinants of PF-4var levels (median 10 ng/ml; interquartile range 8-16 ng/ml) were age, gender and circulating platelet number. Patients who experienced cardiac events (n = 20) during follow-up showed lower levels of PF-4var (8.5 [5.3-10] ng/ml versus 12 [8-16] ng/ml, p = 0.033). ROC analysis for events showed an area under the curve (AUC) of 0.82 (95% CI 0.73-0.90, p<0.001) for higher NT-proBNP levels and an AUC of 0.32 (95% CI 0.19-0.45, p = 0.009) for lower PF-4var levels. Cox proportional hazard analysis showed that PF-4var has an independent prognostic value on top of NT-proBNP. Conclusions: We conclude that low PF-4var/CXCL4L1 levels are associated with a poor outcome in patients with stable CAD and preserved LV function. This prognostic value is independent of NT-proBNP levels, suggesting that both neurohormonal and platelet-related factors determine outcome in these patients.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
VARIANT, CELLS, IN-VIVO, HUMAN MONOCYTES, CXC-CHEMOKINE PLATELET-FACTOR-4, DIFFERENTIATION, CXCL4L1, ANGIOGENESIS, MACROPHAGES, INHIBITION
journal title
PLOS ONE
PLoS One
volume
7
issue
2
article_number
e31343
pages
8 pages
Web of Science type
Article
Web of Science id
000302916100018
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
3.73 (2012)
JCR rank
7/56 (2012)
JCR quartile
1 (2012)
ISSN
1932-6203
DOI
10.1371/journal.pone.0031343
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
3033039
handle
http://hdl.handle.net/1854/LU-3033039
date created
2012-10-23 10:01:57
date last changed
2012-10-23 10:19:16
@article{3033039,
  abstract     = {Background: Platelet-derived chemokines are implicated in several aspects of vascular biology. However, for the chemokine platelet factor 4 variant (PF-4var/CXCL4L1), released by platelets during thrombosis and with different properties as compared to PF-4/CXCL4, its role in heart disease is not yet studied. We evaluated the determinants and prognostic value of the platelet-derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary artery disease (CAD). 
Methodology/Principal Findings: From 205 consecutive patients with stable CAD and preserved left ventricular (LV) function, blood samples were taken at inclusion and were analyzed for PF-4var, RANTES, platelet factor-4 and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Patients were followed (median follow-up 2.5 years) for the combined endpoint of cardiac death, non-fatal acute myocardial infarction, stroke or hospitalization for heart failure. Independent determinants of PF-4var levels (median 10 ng/ml; interquartile range 8-16 ng/ml) were age, gender and circulating platelet number. Patients who experienced cardiac events (n = 20) during follow-up showed lower levels of PF-4var (8.5 [5.3-10] ng/ml versus 12 [8-16] ng/ml, p = 0.033). ROC analysis for events showed an area under the curve (AUC) of 0.82 (95\% CI 0.73-0.90, p{\textlangle}0.001) for higher NT-proBNP levels and an AUC of 0.32 (95\% CI 0.19-0.45, p = 0.009) for lower PF-4var levels. Cox proportional hazard analysis showed that PF-4var has an independent prognostic value on top of NT-proBNP. 
Conclusions: We conclude that low PF-4var/CXCL4L1 levels are associated with a poor outcome in patients with stable CAD and preserved LV function. This prognostic value is independent of NT-proBNP levels, suggesting that both neurohormonal and platelet-related factors determine outcome in these patients.},
  articleno    = {e31343},
  author       = {De Sutter, Johan and van de Veire, Nico R and Struyf, Sofie and Philipp{\'e}, Jan and DE BUYZERE, MARC and Van Damme, Jo},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keyword      = {VARIANT,CELLS,IN-VIVO,HUMAN MONOCYTES,CXC-CHEMOKINE PLATELET-FACTOR-4,DIFFERENTIATION,CXCL4L1,ANGIOGENESIS,MACROPHAGES,INHIBITION},
  language     = {eng},
  number       = {2},
  pages        = {8},
  title        = {PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function},
  url          = {http://dx.doi.org/10.1371/journal.pone.0031343},
  volume       = {7},
  year         = {2012},
}

Chicago
De Sutter, Johan, Nico R van de Veire, Sofie Struyf, Jan Philippé, Marc De Buyzere, and Jo Van Damme. 2012. “PF-4var/CXCL4L1 Predicts Outcome in Stable Coronary Artery Disease Patients with Preserved Left Ventricular Function.” Plos One 7 (2).
APA
De Sutter, J., van de Veire, N. R., Struyf, S., Philippé, J., De Buyzere, M., & Van Damme, J. (2012). PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function. PLOS ONE, 7(2).
Vancouver
1.
De Sutter J, van de Veire NR, Struyf S, Philippé J, De Buyzere M, Van Damme J. PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function. PLOS ONE. 2012;7(2).
MLA
De Sutter, Johan, Nico R van de Veire, Sofie Struyf, et al. “PF-4var/CXCL4L1 Predicts Outcome in Stable Coronary Artery Disease Patients with Preserved Left Ventricular Function.” PLOS ONE 7.2 (2012): n. pag. Print.