Associations between the IL-6-neutralizing sIL-6R-sgp130 buffer system and coronary artery disease in postmenopausal women

Abstract

BACKGROUND As a major inflammatory pathway in coronary artery disease (CAD), IL-6 trans-signaling is activated by the IL-6: sIL-6Rα binary complex (B) and inhibited by sgp130 through forming the IL-6: sIL-6Rα: sgp130 ternary complex (T). The aim of the present study was to examine the possible relationship between biomarkers mirroring the IL-6-neutralizing sIL-6R-sgp130 buffer system and CAD in postmenopausal women. METHODS Our study recruited 155 CAD patients and 181 controls among postmenopausal women. Circulating levels of IL-6, sIL-6Rα and sgp130 were detected using an enzyme-linked immunosorbent assay, and the B/T ratio was calculated by the specific formulas. RESULTS CAD patients showed significantly higher circulating levels of IL-6 and sIL-6Rα, significantly higher B/T ratio, and significantly lower sgp130 levels than controls (all P<0.05). Spearman's correlation analysis indicated that IL-6 levels (r=0.185, P<0.01) and B/T ratio (r=0.319, P<0.01) were positively related to Gensini scores, while elevated sgp130 levels were significantly associated with decreased Gensini scores (r=-0.565, P<0.001). In addition, multiple regression analysis showed that Gensini scores were negatively associated with serum sgp130 levels (β-coefficient =-0.318, P<0.001) and had a positive association with IL-6 levels (β-coefficient =0.138, P<0.05). Multivariate logistic regression analysis identified that after adjusting for confounding factors, higher sgp130 remained an independent predictor of lower incidence of CAD in women after menopause (OR =0.904; 95% CI: 0.837-0.976, P=0.010). Moreover, sgp130 levels at 136.01 ng/mL (AUC =0.957, 95% CI: 0.928-0.986, P<0.001) and B/T ratio at 1.51 (AUC =0.765; 95% CI: 0.702-0.828, P<0.001) were effective cut-off points to determine the presence of CAD based on receiver operating characteristic curves. CONCLUSIONS Based on this small case-control study, sgp130 and B/T ratio in the IL-6-neutralizing sIL-6R-sgp130 buffer system may be promising biomarkers for CAD diagnosis and assessments of coronary stenosis severity in postmenopausal women.