Elevated serum osteopontin (SPP1) levels are independently associated with imaging-defined plaque vulnerability and short-term cardiovascular events in patients with coronary artery disease, with MMP-9 partially mediating the association between SPP1 and plaque vulnerability.
Key Findings
Results
Serum SPP1 levels were significantly higher in patients with vulnerable plaques compared to those with stable plaques.
Mean SPP1 was 55.85 ± 12.26 ng/mL in the vulnerable plaque group versus 39.18 ± 9.42 ng/mL in the stable plaque group.
The difference was statistically significant (P < 0.001).
Plaque classification was based on IVUS/OCT intravascular imaging.
The study included 300 patients total, with 150 classified as having vulnerable plaques.
Results
Elevated SPP1 levels were independently associated with plaque vulnerability in multivariable logistic regression analysis.
OR = 1.08 per unit increase in SPP1 (95% CI: 1.05–1.11; P < 0.001).
The association remained significant after multivariable adjustment.
This was a prospective observational cohort study design.
Results
SPP1 demonstrated superior discriminatory performance for identifying vulnerable plaques by ROC analysis.
AUC = 0.875 (95% CI: 0.837–0.913) for SPP1 in distinguishing vulnerable from stable plaques.
ROC analysis was performed alongside multivariable regression and survival analyses.
Results
Higher baseline SPP1 levels were independently associated with major adverse cardiovascular events (MACE) during 6-month follow-up.
HR = 1.35 (95% CI: 1.11–1.64; P = 0.002) in multivariable Cox regression.
Kaplan-Meier analysis showed significantly lower MACE-free survival in the high SPP1 group (log-rank P = 0.004).
Participants were followed for 6 months to record MACE.
Results
SPP1 was significantly associated with inflammatory biomarkers MMP-9, IL-6, and hsCRP in multivariable analyses.
SPP1 was most strongly associated with MMP-9 (β = 0.71, P < 0.01).
Association with IL-6 was also significant (β = 0.42, P < 0.01).
Association with hsCRP was weaker (β = 0.08, P < 0.01).
Results
MMP-9 partially mediated the association between SPP1 and coronary plaque vulnerability.
Mediation analysis indicated MMP-9 accounted for 44.2% of the total effect of SPP1 on plaque vulnerability.
The mediation was described as partial, indicating SPP1 also has direct associations with plaque vulnerability independent of MMP-9.
Wang X. (2026). Serum osteopontin is associated with coronary plaque vulnerability and short-term cardiovascular events: a prospective cohort study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1771524