Objective: The role of C-X-C motif chemokine 12 (CXCL12) in atherosclerotic cardiovascular diseases (ASCVDs) has emerged as one of the research hotspots in recent years. Studies reported that the higher blood CXCL12 level was associated with increased major adverse cardiovascular events (MACEs), but the results were inconsistent. The objective of this study was to clarify the prognostic value of the blood CXCL12 level in patients with coronary artery disease (CAD) through meta-analysis.

Methods: All related studies about the association between the blood CXCL12 level and the prognosis of CAD were comprehensively searched and screened according to inclusion criteria and exclusion criteria. The quality of the included literature was evaluated using the Newcastle-Ottawa Scale (NOS). The heterogeneity test was conducted, and the pooled hazard risk (HR) or the odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed-effect or random-effects model accordingly. Publication bias was evaluated using Begg's funnel plot and Egger's test. Sensitivity analysis and subgroup analysis were also conducted.

Results: A total of 12 original studies with 2,959 CAD subjects were included in the final data combination. The pooled data indicated a significant association between higher CXCL12 levels and MACEs both in univariate analysis (HR 5.23, 95% CI 2.48-11.04) and multivariate analysis (HR 2.53, 95% CI 2.03-3.16) in the CXCL12 level as the category variable group. In the CXCL12 level as the continuous variable group, the result also indicated that the higher CXCL12 level significantly predicted future MACEs (multivariate OR 1.55, 95% CI 1.02-2.35). Subgroup analysis of the CXCL12 level as the category variable group found significant associations in all acute coronary syndrome (ACS) (univariate HR 9.72, 95% CI 4.69-20.15; multivariate HR 2.47, 95% CI 1.79-3.40), non-ACS (univariate HR 2.73, 95% CI 1.65-4.54; multivariate HR 3.49, 95% CI 1.66-7.33), Asian (univariate HR 7.43, 95% CI 1.70-32.49; multivariate HR 2.21, 95% CI 1.71-2.85), Caucasian (univariate HR 3.90, 95% CI 2.73-5.57; multivariate HR 3.87, 95% CI 2.48-6.04), short-term (univariate HR 9.36, 95% CI 4.10-21.37; multivariate HR 2.72, 95% CI 1.97-3.76), and long-term (univariate HR 2.86, 95% CI 1.62-5.04; multivariate HR 2.38, 95% CI 1.76-3.22) subgroups. Subgroup analysis of the CXCL12 level as the continuous variable group found significant associations in non-ACS (multivariate OR 1.53, 95% CI 1.23-1.92), Caucasian (multivariate OR 3.83, 95% CI 1.44-10.19), and long-term (multivariate OR 1.62, 95% CI 1.37-1.93) subgroups, but not in ACS (multivariate OR 1.36, 95% CI 0.67-2.75), Asian (multivariate OR 1.40, 95% CI 0.91-2.14), and short-term (multivariate OR 1.16, 95% CI 0.28-4.76) subgroups. No significant publication bias was found in this meta-analysis.

Conclusion: The higher blood CXCL12 level is associated with increased MACEs in patients with CAD, and the blood CXCL12 level may serve as an important prognostic index for CAD. Integrating the blood CXCL12 level into CAD risk assessment tools may provide more comprehensive messages for evaluating and managing patients with CAD.