Serum Osteopontin Is Associated with Coronary Plaque Vulnerability and Short-Term Cardiovascular Events: A Prospective Cohort Study

Abstract

Abstract Background: Coronary plaque vulnerability underlies acute coronary events, yet reliable identification of high-risk plaques in clinical practice remains limited. Osteopontin (SPP1) is an immuno-inflammatory glycoprotein involved in atherosclerosis, but its relevance to plaque vulnerability and short-term cardiovascular events is not fully defined. Methods: In this prospective observational cohort study, a total of 300 patients were included, of whom 150 were classified as having vulnerable plaques based on IVUS/OCT imaging. Serum SPP1 and inflammatory biomarkers were measured at baseline. Plaques were classified as stable or vulnerable based on intravascular imaging. Participants were followed for 6 months to record major adverse cardiovascular events (MACE). Multivariable regression, receiver operating characteristic (ROC) analysis, survival analysis, and mediation analysis were performed to evaluate associations among SPP1, plaque vulnerability, inflammatory markers, and short-term cardiovascular events. Results: Serum SPP1 levels were significantly higher in patients with vulnerable plaques than in those with stable plaques (55.85 ± 12.26 vs. 39.18 ± 9.42 ng/mL; P < 0.001). In multivariable analyses, SPP1 was strongly associated with MMP-9 (β = 0.71) and IL-6 (β = 0.42), with a weaker association with hsCRP (β = 0.08) (all P < 0.01). In multivariable logistic regression analyses, elevated SPP1 levels were independently associated with plaque vulnerability (OR = 1.08 per unit increase; 95% CI: 1.05–1.11; P < 0.001). Receiver operating characteristic analysis demonstrated that SPP1 showed superior discriminatory performance for vulnerable plaques (AUC = 0.875, 95% CI: 0.837–0.913). During the 6-month follow-up, higher baseline SPP1 levels were independently associated with MACE (HR = 1.35; 95% CI: 1.11–1.64; P = 0.002), and Kaplan–Meier analysis showed significantly lower MACE-free survival in the high SPP1 group (log-rank P = 0.004). Mediation analysis further indicated that MMP-9 partially mediated the association between SPP1 and plaque vulnerability, accounting for 44.2% of the total effect. Conclusion: Elevated serum SPP1 levels are independently associated with imaging-defined plaque vulnerability and short-term cardiovascular events in patients with coronary artery disease. Serum SPP1 may serve as a clinically relevant biomarker reflecting immuno-inflammatory plaque instability, warranting further validation in larger cohorts.