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Cited by 13Atherosclerosis and Cardiovascular DiseasesChemokine receptors and signalingInflammatory Biomarkers in Disease Prognosis

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The role of blood CXCL12 level in prognosis of coronary artery disease: A meta-analysis

Open access
Zhang, Shunrong, Ding, Yu, Feng, Fei, Gao, Yue·2022·Frontiers in Cardiovascular Medicine
DOI 10.3389/fcvm.2022.938540PMC PMC9363627
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Abstract

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.

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Figure 1 Flow diagram of the study selection process.
Figure 1 Flow diagram of the study selection process.CC BY · PubMed Central
Figure 2 Forest plot of the association between C-X-C motif chemokine 12 (CXCL12) level as category variable and major adverse cardiovascular events (MACEs) in patients with coronary artery disease (CAD) (univariate analysis).
Figure 2 Forest plot of the association between C-X-C motif chemokine 12 (CXCL12) level as category variable and major adverse cardiovascular events (MACEs) in patients with coronary artery disease (CAD) (univariate analysis).CC BY · PubMed Central
Figure 3 Forest plot of the association between CXCL12 level as category variable and MACEs in patients with CAD (multivariate analysis).
Figure 3 Forest plot of the association between CXCL12 level as category variable and MACEs in patients with CAD (multivariate analysis).CC BY · PubMed Central
Figure 4 Forest plot of the association between CXCL12 level as continuous variable and MACEs in patients with CAD (multivariate analysis).
Figure 4 Forest plot of the association between CXCL12 level as continuous variable and MACEs in patients with CAD (multivariate analysis).CC BY · PubMed Central
Figure 5 Begg's funnel plot for evaluating publication bias of included studies. (A) Univariate analysis in CXCL12 level as category variable group (Z = 1.13, P = 0.26); (B) multivariate analysis in CXCL12 level as category variable group (Z = 1.71, P = 0.086); (C) and multivariate analysis in CXCL12 level as continuous variable group (Z = 0.75, P = 0.452).
Figure 5 Begg's funnel plot for evaluating publication bias of included studies. (A) Univariate analysis in CXCL12 level as category variable group (Z = 1.13, P = 0.26); (B) multivariate analysis in CXCL12 level as category variable group (Z = 1.71, P = 0.086); (C) and multivariate analysis in CXCL12 level as continuous variable group (Z = 0.75, P = 0.452).CC BY · PubMed Central
Figure 6 Sensitivity analysis evaluating the influence of any single study on the overall effects. (A) Univariate analysis data of the CXCL12 level as category variable group. (B) Multivariate analysis data of the CXCL12 level as category variable group; (C) Multivariate analysis data of the CXCL12 level as the continuous variable group.
Figure 6 Sensitivity analysis evaluating the influence of any single study on the overall effects. (A) Univariate analysis data of the CXCL12 level as category variable group. (B) Multivariate analysis data of the CXCL12 level as category variable group; (C) Multivariate analysis data of the CXCL12 level as the continuous variable group.CC BY · PubMed Central

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Citations

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Metadata

Authors
Zhang, S., Ding, Y., Feng, F., & Gao, Y.
Affiliations
Zhejiang University (CN)
Corresponding author
Gao, Yue
ORCID
Venue
Frontiers in Cardiovascular Medicine
Publisher
Frontiers Media SA
Published
2022-07-27
Volume
9
Pages
938540-938540
ISSN
2297-055X (ISSN-L)
DOI
10.3389/fcvm.2022.938540
PMC
PMC9363627
OpenAlex
W4288033470
Cited by
13
References
2
Citations by year
2026: 4 · 2025: 4 · 2024: 4 · 2023: 1
FWCI
0.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cardiovascular Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
Keywords
CXCL12, coronary artery disease, prognostic factors, major adverse cardiovascular events, acute coronary syndrome, atherosclerotic cardiovascular disease, serum chemokine levels, risk stratification, risk reclassification, risk prediction model

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