title: PF-4var/CXCL4L1 predicts outcome in stable coronary artery disease patients with preserved left ventricular function.
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).
  
  
  RESULTS
  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.
authors.affiliation: Department of Cardiology, AZ Maria Middelares Ghent, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: De Sutter
authors.forename: Nico R
authors.initials: NR
authors.lastname: Van de Veire
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Jan
authors.initials: J
authors.lastname: Philippé
authors.forename: Marc
authors.initials: M
authors.lastname: De Buyzere
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D018946:Chemokine CCL5 / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010978:Platelet Factor 4 / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D015203:Reproducibility of Results; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000235:genetics*
chemical_list: D018946:Chemokine CCL5; C064936:PF4V1 protein, human; D010978:Platelet Factor 4