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 to 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.

β‐blockers interfere with cell homing receptors and regulatory proteins in a model of spontaneously hypertensive rats

“…It is known, however, that SDF‐1 levels are increased in hypertensive states, and that the greater the cardiovascular involvement, the higher SDF‐1 levels . Increased levels of SDF‐1 are also associated with adverse cardiovascular outcomes in individuals with coronary artery disease . Furthermore, increased plasma levels of SDF‐1 are associated with increased mobilization of hematopoietic stem cells, which apparently was not impaired in our study, though other studies have shown a negative effect of propranolol on in vitro cell proliferation …”

“…22 Increased levels of SDF-1 are also associated with adverse cardiovascular outcomes in individuals with coronary artery disease. 23 Furthermore, increased plasma levels of SDF-1 are associated with increased mobilization of hematopoietic stem cells, 24 which apparently was not impaired in our study, though other studies have shown a negative effect of propranolol on in vitro cell proliferation. 25 We found no significant differences when we examined specific homing receptors, CXCR-4 and CXCR-7.…”

MIF and CXCL12 in Cardiovascular Diseases: Functional Differences and Similarities

“…Therefore determination of CXCL12 might be very useful as early additional biomarker ( 11 ). Recently, it was shown that CXCL12 is also associated with heart failure ( 137 ), and that plasma CXCL12 levels are even superior to ­traditional risk factors in predicting adverse cardiovascular outcomes ( 10 ). Although there are still some contradictory clinical results, it is clear that CXCL12 does play a role in atherosclerosis and CVD.…”

Circulating Stromal Cell-Derived Factor 1α Levels in Heart Failure: A Matter of Proper Sampling

“…In recent years, the chemokine Stromal cell-Derived Factor 1α (SDF1α or CXCL12) has been shown to play a role in cardiovascular diseases [ 1 ] and to be a promising biomarker [ 2 , 3 ]. Together with its receptor, CXCR4, SDF1α is involved in the homing of progenitor/stem cells thereby favoring the repair of injured myocardium through angiogenesis [ 1 , 4 – 6 ].…”