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Elevated Circulating HMGB1 Levels as a Potential Biomarker for the Diagnosis and Therapy of Heart Failure: A
Xiaoting Jiang1,2,3, Xia Feng1, Wen Liu1
1Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China.
Insights
Elevated levels of High-mobility group box 1 (HMGB1) are linked to heart failure (HF) development. HMGB1 may serve as a biomarker for predicting HF risk and guiding new treatment strategies.
Area of Science:
- Cardiovascular Medicine
- Biomarkers
- Inflammation
Background:
- High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) implicated in cardiovascular diseases.
- The role of HMGB1 in heart failure (HF) pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the association between circulating HMGB1 levels and the occurrence of HF.
- To evaluate HMGB1 as a potential biomarker for HF development.
Main Methods:
- A cross-sectional study of 343 patients (151 with HF, 192 controls) presenting with chest symptoms.
- HMGB1 levels were measured and correlated with HF occurrence using Spearman analysis, logistic regression, RCS plots, and ROC curves.
Main Results:
- Serum HMGB1 levels were significantly higher in HF patients compared to controls (1.53 vs 0.93 ng/mL).
- HMGB1 showed positive correlations with LVEDD, LAD, SIRI, and negative correlation with LVEF.
- Elevated HMGB1 was independently associated with increased HF risk (aOR=2.273) and demonstrated good predictive value (AUC=0.736).
- A combined model including HMGB1 and other parameters achieved superior prediction (AUC=0.807).
Conclusions:
- Elevated HMGB1 levels are significantly associated with the occurrence of heart failure.
- HMGB1 may serve as a valuable biomarker for predicting HF risk and developing novel therapeutic strategies.
Background:
High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP), has increasingly been implicated in the pathogenesis of various cardiovascular diseases. This study aimed to elucidate the relationship between circulating HMGB1 levels and the development of heart failure (HF).
Methods:
This single-center cross-sectional study enrolled 412 patients presenting with chest tightness or pain at the Department of Cardiovascular Medicine, First Affiliated Hospital of Nanchang University, between January and July 2025. The relationship between HMGB1 and HF occurrence was evaluated using Spearman's correlation analysis, logistic regression models, restricted cubic spline (RCS) plots, and receiver operating characteristic (ROC) curves. Subgroup analyses were also performed to assess the robustness of the findings.
Results:
Of the 412 enrolled patients, 343 were included in the final analysis after application of the exclusion criteria; 151 were diagnosed with HF, and 192 served as controls. Serum HMGB1 levels were significantly higher in the HF group than in the control group (1.53 ng/mL vs 0.93 ng/mL; p < 0.001). Spearman's correlation analysis revealed significant positive correlations between HMGB1 levels and left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), and the systemic inflammatory response index (SIRI), and a significant negative correlation with left ventricular ejection fraction (LVEF) (all p < 0.05). In the univariate logistic regression analysis, elevated HMGB1 levels were strongly associated with increased HF risk (odds ratio [OR] = 2.942, 95% confidence interval [CI]: 2.113-4.095; p < 0.001). This association remained significant in multivariable models after sequential adjustment for demographic, clinical, and laboratory covariates, with a fully adjusted OR of 2.273 (95% CI: 1.410-3.663; p < 0.001). Restricted cubic spline (RCS) analysis confirmed a linear dose-response relationship between HMGB1 levels and HF risk (p for nonlinearity = 0.174). ROC analysis showed that HMGB1 alone had good predictive value for HF (area under the curve [AUC] = 0.736), outperforming individual traditional markers. Furthermore, a combined model incorporating HMGB1, LVEF, LVEDD, LAD, and SIRI achieved superior predictive accuracy (AUC = 0.807). Finally, subgroup analyses showed that only sex exhibited a significant interaction, while interactions for all other variables were non significant interaction ( p for interaction > 0.05), indicating that this relationship was robust and independent of major clinical variables.
Conclusions:
The levels of HMGB1 elevation were significantly related to the occurrence of HF, which may serve as a potential biomarker for the development of innovative therapeutic strategies in patients with heart failure.
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