Plasma stromal cell-derived factor 1α/CXCL12 level predicts long-term adverse cardiovascular outcomes in patients with coronary artery disease

• Published in: Atherosclerosis Vol. 238; no. 1; pp. 113 - 118
• Main Authors: Ghasemzadeh, Nima, Hritani, Abdul Wahab, De Staercke, Christine, Eapen, Danny J, Veledar, Emir, Al Kassem, Hatem, Khayata, Mohamed, Zafari, A.Maziar, Sperling, Laurence, Hooper, Craig, Vaccarino, Viola, Mavromatis, Kreton, Quyyumi, Arshed A
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.01.2015
• Subjects: Aged; Area Under Curve; Cardiovascular; Cardiovascular Diseases - blood; Cardiovascular Diseases - therapy; Cardiovascular outcomes; Chemokine CXCL12 - blood; Cohort Studies; Coronary Angiography; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - therapy; CXCL12; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stromal cell-derived factor1α; Treatment Outcome; Cardiovascular outcomes; CXCL12; Stromal cell-derived factor1α; Coronary artery disease
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2014.10.094

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. Conclusion : Plasma CXCL12 level is a strong independent predictor of adverse cardiovascular outcomes in patients with CAD and improves risk reclassification.