Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients.

Objective: This cross-sectional study tested the hypothesis that increased serum level of high mobility group box-1 protein (HMGB1), a pro-inflammatory ligand of receptor for advanced glycation end products (RAGE), is associated with coronary artery disease (CAD) in nondiabetic and type 2 diabetic patients.

Methods: Serum levels of HMGB1, endogenous secretory RAGE (esRAGE), soluble RAGE (sRAGE) and inflammatory cytokines were determined in 512 patients categorized as Group I (n=132, without diabetes and CAD), Group II (n=149, with CAD but no diabetes), Group III (n=80, with diabetes but no CAD) and Group IV (n=151, with diabetes and CAD).

Results: Serum levels of HMGB1 and hsCRP were higher in Group II than in Group I, and in Group IV than in Group III (all P<0.001). HMGB1 was positively related to hsCRP, TNF-alpha and IL-6 levels in the whole subjects (all P<0.01). Group II patients had lower sRAGE (P=0.058) and esRAGE (P<0.001) levels versus those in Group I. However, in the diabetic patients, those in Group IV had lower esRAGE (P<0.001) but higher sRAGE (P=0.002) levels compared to those in Group III. In multivariable regression analysis, HMGB1, esRAGE and conventional risk factors (age, smoking, hypertension, HDL-C, hsCRP, TNF-alpha) were independent determinants of CAD in nondiabetic patients. Moreover, HMGB1 and esRAGE consistently remained to be independently associated with CAD in diabetic patients, so did other major conventional risk factors.

Conclusion: This study demonstrates that increased serum HMGB1 level is associated with CAD in nondiabetic and type 2 diabetic patients.