Baseline Serum HMGB1 and the Composite of All-Cause Mortality or First Heart Failure Rehospitalization in Heart Failure with Preserved Ejection Fraction.

Purpose: To evaluate the association between baseline serum high mobility group box 1 (HMGB1) and the composite of all-cause mortality or first heart failure rehospitalization in patients with heart failure with preserved ejection fraction (HFpEF). Patients and Methods: This single-center prospective cohort included 224 patients with HFpEF. The primary endpoint was the first occurrence of all-cause mortality or heart failure rehospitalization. Results: During a median observation time of 58 months, 37 of 224 patients (16.5%) experienced the composite endpoint. Baseline HMGB1 was higher in patients with events than in those without events (8.76 ± 3.18 vs 5.99 ± 1.86 µg/L; P<0.001). After adjustment for NT-proBNP, age, and sex, each 1 µg/L increase in HMGB1 was associated with a higher risk of the composite endpoint (hazard ratio, 1.399; 95% confidence interval [CI], 1.242-1.576; P<0.001). Apparent areas under the curve were 0.753 (95% CI, 0.653-0.853) for HMGB1, 0.790 (95% CI, 0.708-0.872) for NT-proBNP, and 0.870 (95% CI, 0.793-0.947) for their combination. The combination did not significantly outperform NT-proBNP alone (ΔAUC, 0.080; 95% CI, -0.012 to 0.171; nominal P=0.088; Holm-adjusted P=0.176). The optimism-corrected Cox concordance index was 0.828, and sensitivity analyses showed associations in the same direction. Conclusion: Higher baseline serum HMGB1 was associated with the composite of all-cause mortality or first heart failure rehospitalization in this exploratory HFpEF cohort. Incremental discrimination beyond NT-proBNP and clinical utility remain unestablished. Independent prospective multicenter validation is required.