Abstract 3213: Clinical Significance of Circulating Concentration of High-Mobility Group Box 1 (HMGB1) in Patients with Acute Coronary Syndrome
High-mobility group box 1 (HMGB1) functions as a proinflammatory cytokine when actively secreted during cell activation or passively released from necrotic cells. Recent studies have suggested that HMGB1 produced by activated vascular smooth cells may contribute to the progression and vulnerability of human atherosclerotic lesions toward rupture. Thus, we evaluated the clinical significance of serum HMGB1 in patients with acute coronary syndrome (ACS).
Methods: We measured serum HMGB1 with a recently developed ELISA ( Clin Chim Acta 2006;372:173) on admission in 297 patients hospitalized for ACS within 24 hrs (mean, 6.7 hrs) after the onset of chest pain [ST-segment elevation ACS (STE-ACS), 144 patients]. Also, HMGB1 were measured in 60 patients with stable angina pectoris and 40 age-matched healthy volunteers.
Results: Patients with STE-ACS (39%) and those with non-ST-segment elevation ACS (NSTE-ACS, 31%) had significantly (P<0.0001) higher percentage of elevated HMGB1 (> the lower detection limit of 0.3 ng/ml) than those with stable angina pectoris (3%) and healthy volunteers (0%). Patients with elevated HMGB1 were older, and had higher concentrations of high-sensitive C-reactive protein (Hs-CRP) and BNP than those without (Table⇓). There were 18 in-hospital deaths in patients with ACS. On a stepwise Cox regression analysis including 10 clinical and biochemical variables, elevated HMGB1 (relative risk [RR] 7.12; P = 0.01), age (RR 1.15; P = 0 .002), and elevated troponin I (> the median of 0.33 ng/ml; RR 11.4; P = 0.02) were independent predictors of in-hospital mortality. Patients with elevated HMGB1 had a higher in-hospital mortality rate than those without elevated HMGB1 in patients with STE-ACS (21% vs 1%, P<0.0001) and those with NSTE-ACS (8% vs 1%, P = 0.03).
Conclusion: HMGB1 concentrations are elevated on admission in patients with ACS, and elevated HMGB1 may be independently associated with an increased risk of in-hospital mortality in this population.