title: Plasma stromal cell-derived factor 1α/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease.
abstract: OBJECTIVE
  Stromal derived factor-1α/CXCL12 is a chemoattractant responsible for homing of progenitor cells to ischemic tissues. We aimed to investigate the association of plasma CXCL12 with long-term cardiovascular outcomes in patients with coronary artery disease (CAD).
  
  
  METHODS
  785 patients aged: 63 ± 12 undergoing coronary angiography were independently enrolled into discovery (N = 186) and replication (N = 599) cohorts. Baseline levels of plasma CXCL12 were measured using Quantikine CXCL12 ELISA assay (R&D systems). Patients were followed for cardiovascular death and/or myocardial infarction (MI) for a mean of 2.6 yrs. Cox proportional hazard was used to determine independent predictors of cardiovascular death/MI.
  
  
  RESULTS
  The incidence of cardiovascular death/MI was 13% (N = 99). High CXCL12 level based on best discriminatory threshold derived from the ROC analysis predicted risk of cardiovascular death/MI (HR = 4.81, p = 1 × 10(-6)) independent of traditional risk factors in the pooled cohort. Addition of CXCL12 to a baseline model was associated with a significant improvement in c-statistic (AUC: 0.67-0.73, p = 0.03). Addition of CXCL12 was associated with correct risk reclassification of 40% of events and 10.5% of non-events. Similarly for the outcome of cardiovascular death, the addition of the CXCL12 to the baseline model was associated with correct reclassification of 20.7% of events and 9% of non-events. These results were replicated in two independent cohorts.
  
  
  CONCLUSIONS
  Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Nima
authors.initials: N
authors.lastname: Ghasemzadeh
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Abdul Wahab
authors.initials: AW
authors.lastname: Hritani
authors.affiliation: Center for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: De Staercke
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Eapen
authors.affiliation: Department of Biostatistics, Florida International University, Miami, FL, USA; Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Emir
authors.initials: E
authors.lastname: Veledar
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Hatem
authors.initials: H
authors.lastname: Al Kassem
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khayata
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors.forename: A Maziar
authors.initials: AM
authors.lastname: Zafari
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Sperling
authors.affiliation: Center for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Hooper
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA; Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.
authors.forename: Viola
authors.initials: V
authors.lastname: Vaccarino
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA, USA.
authors.forename: Kreton
authors.initials: K
authors.lastname: Mavromatis
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA. Electronic address: aquyyum@emory.edu.
authors.forename: Arshed A
authors.initials: AA
authors.lastname: Quyyumi
mesh_terms: D000368:Aged; D019540:Area Under Curve; D002318:Cardiovascular Diseases / Q000097:blood / Q000628:therapy*; D054377:Chemokine CXCL12 / Q000097:blood*; D015331:Cohort Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12
keywords: CXCL12; Cardiovascular outcomes; Coronary artery disease; Stromal cell-derived factor1α