Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction

Objective: High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern molecule, which suggests a potential role of this protein in the pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been shown to be independently associated with cardiac mortality in ST-segment elevation myocardial infarction. However, its prognostic value remains unclear in unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). Methods: HMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I and B-type natriuretic peptide concentrations were measured on admission in 258 consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24. h (mean, 7.4. h) of the onset of chest symptoms. Results: A total of 38 (14.7%) cardiovascular deaths, including 10 in-hospital deaths, occurred during a median follow-up period of 49 months after admission. In a stepwise Cox regression analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk (RR) 3.24 per 10-fold increment; P=. 0.0003], cardiac troponin I (RR 1.83 per 10-fold increment, P=. 0.0007), Killip class. >. 1 (RR 4.67, P=. 0.0001) and age (RR 1.05 per 1-year increment, P=. 0.03), but not hsCRP, were independently associated with cardiovascular mortality. In-hospital and cardiovascular mortality rates were higher in patients with increased HMGB1 (≥2.4. ng/mL of median value) than those without increased HMGB1 (6.3% vs. 1.5%, P=. 0.04; and 23% vs. 6.9%, P=. 0.0003). Conclusion: Circulating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24. h of onset.