HMGB1 is an independent predictor of death and heart transplantation in heart failure.
BACKGROUND
High-Mobility-Group Box 1 (HMGB1) has been established as an important mediator of myocardial inflammation and associated with progression of heart failure (HF). The aim of this study was to analyze the prognostic value of systemic HMGB1 levels in HF patients with ischemic and non-ischemic cardiomyopathy.


RESULTS
We conducted an analysis (median follow-up time 2.5 years) of HMGB1 plasma concentration in 154 patients with systolic HF and correlated the results with disease severity and prognosis. HMGB1 in HF patients with severe symptoms (NYHA III/IV; 5.35 ng/ml; interquartile range (IQR) = 3.48-8.42 ng/ml) was significantly elevated compared with that in patients with mild symptoms (NYHA I/II; 3.37 ng/ml, IQR = 2.31-5.22 ng/ml, p < 0.0001) and with controls (3.25 ng/ml, IQR = 3.04-3.67 ng/ml, p < 0.0001). HMGB1 levels correlated with other markers of heart failure indicating an association of HMGB1 with disease severity in HF. In a univariate cox regression model for the combined endpoint of death and heart transplantation, HMGB1 proved to be a predictor at cut-off values based on HMGB1 terciles of either 3.4 or 6.1 ng/ml (p = 0.001 and p < 0.0001, respectively). In a multivariate cox regression model, which included NT-proBNP, creatinine, age, NYHA class, white blood cell count, anemia, and age, HMGB1 remained an independent predictor of the combined endpoint (hazard ratio (HR) = 2.48, 95% confidence interval (CI) = 1.06-5.83, p = 0.037 and HR = 2.48, 95% CI = 1.31-4.71, p = 0.005, respectively).


CONCLUSIONS
Our findings demonstrate that HMGB1 plasma concentration is elevated in HF and correlates with disease severity and that is an independent predictor of the combined endpoint death and heart transplantation in HF patients.
Department of Internal Medicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
H C
HC
Volz
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D
Laohachewin
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D
Schellberg
A R
AR
Wienbrandt
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M
Nelles
C
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Zugck
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Z
Kaya
H A
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Katus
M
M
Andrassy
D000368:Aged; D009202:Cardiomyopathies / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D024243:HMGB1 Protein / Q000097:blood*; D054143:Heart Failure, Systolic / Q000401:mortality / Q000503:physiopathology* / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000503:physiopathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
D024243:HMGB1 Protein