title: Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction.
abstract: 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 24h (mean, 7.4h) 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).
  
  
  CONCLUSIONS
  Circulating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24h of onset.
authors.affiliation: Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Tousei
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Junnichi
authors.initials: J
authors.lastname: Ishii
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kitagawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Kousuke
authors.initials: K
authors.lastname: Hattori
authors.forename: Masanori
authors.initials: M
authors.lastname: Okumura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Naruse
authors.forename: Sadako
authors.initials: S
authors.lastname: Motoyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsui
authors.forename: Ikuko
authors.initials: I
authors.lastname: Tanaka
authors.forename: Hideo
authors.initials: H
authors.lastname: Izawa
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomura
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D017052:Hospital Mortality; D006760:Hospitalization; D006801:Humans; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D019210:Troponin I / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D019210:Troponin I; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein