Association of Gla-Rich Protein (GRP) With Inflammatory Markers in Critically Ill Patients: A Cross-Sectional Observational Study

Abstract

Objectives: Gla-rich protein (GRP), a vitamin K-dependent protein, has been increasingly recognized for its dual role in modulating inflammation and inhibiting pathological calcification. Despite its emerging importance in chronic conditions, limited evidence exists regarding its behavior during acute critical illness. This study aimed to investigate the association between GRP, systemic inflammatory markers, oxidative stress (via total thiol oxidation-reduction ratio, TORR), and calcium metabolism in critically ill patients. Materials and Methods: This cross-sectional observational study included 93 critically ill patients admitted to the intensive care unit (ICU) and 60 age- and sex-matched non-critically ill volunteers. Serum GRP levels were measured using ELISA. Other biomarkers including TORR, C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), immature granulocytes (IGs), and serum calcium were also analyzed. Pearson's correlation, multivariate linear regression, and ROC analysis were performed to assess the relationships among GRP and biochemical markers, as well as their capacity to differentiate ICU patients from controls. Results: GRP, TORR, CRP, PCT, WBC, IGs, and ferritin levels were significantly elevated in ICU patients compared to the control group, whereas serum calcium levels were markedly reduced (all p < 0.05). GRP levels demonstrated moderate positive correlations with WBC (r = 0.47), neutrophils (r = 0.51), TORR (r = 0.42), CRP (r = 0.30), and IGs (r = 0.46), and a strong negative correlation with calcium (r = -0.63). In multivariate regression, TORR, CRP, WBC, IGs, PCT, and calcium levels showed significant correlations with GRP levels in univariate analysis. ROC analysis revealed that CRP had the highest discriminatory power (AUC = 0.88; 95% CI: 0.82-0.94), followed by TORR (AUC = 0.79; 95% CI: 0.71-0.86), GRP (AUC = 0.76; 95% CI: 0.68-0.84), and IGs (AUC = 0.77; 95% CI: 0.69-0.85), for distinguishing ICU patients from non-critically ill individuals. Conclusions: Our findings demonstrated that GRP is significantly associated with systemic inflammation, oxidative stress, and calcium metabolism disturbances in critically ill patients. The combined evaluation of GRP and TORR may enhance the understanding of inflammatory and oxidative mechanisms in acute critical illness. Although this study did not assess patient outcomes, these biomarkers could serve as promising candidates for future prognostic research in ICU settings.