Integrative analysis of systemic biomarkers and carotid plaque instability in patients with atherosclerosis: A retrospective cross-sectional study

Objective Carotid plaque instability is associated with ischemic stroke; however, its relationship with systemic pathways remains incompletely understood. We explored associations between inflammatory, coagulation, metabolic, and renal biomarkers and ultrasound-defined carotid plaque instability. Methods This exploratory, single-center, retrospective cross-sectional association study included patients who underwent carotid ultrasonography between March 2021 and March 2025. Laboratory and imaging variables were compared between stable and unstable plaques. Multivariable logistic regression analyses were performed in four system-specific models adjusted for age, sex, hypertension, and diabetes mellitus, followed by an integrated analysis. The incremental contribution of CRP and eGFR beyond clinical covariates was explored by comparing discrimination and calibration, with bootstrap resampling used to assess optimism. Results 361 patients were included (311 stable; 50 unstable). A history of stroke was more common in the unstable-plaque group (p < 0.05). CRP levels were higher in the unstable-plaque group, whereas eGFR did not differ between groups. In multivariable analyses, no biomarker was independently associated with plaque instability. In the integrated model (n = 326; 43 events), history of stroke was associated with plaque instability (OR = 2.46, 95% CI 1.15–5.25, p = 0.020), whereas CRP (OR = 1.002 per 1 mg/L, 95% CI 0.997–1.007, p = 0.450) and eGFR (OR = 0.999 per 1 mL/min/1.73 m 2 , 95% CI 0.988–1.011, p = 0.913) were not associated. AUCs were 0.704 for the clinical model and 0.709 for the integrated model (ΔAUC = +0.005), indicating minimal incremental discrimination. Conclusions History of stroke was associated with carotid plaque instability, whereas CRP and eGFR were not independently associated after multivariable adjustment. Adding CRP and eGFR to clinical variables provided minimal incremental discrimination, suggesting limited additional value for distinguishing ultrasound-defined plaque instability. Given the cross-sectional design, these findings should be interpreted as associations rather than temporal or causal relationships.