Abstract
PURPOSE: This study aimed to investigate the association between serum high mobility group box 1 (HMGB1) levels and stroke through the long-term follow-up of patients with paroxysmal atrial fibrillation (AF). PATIENTS AND METHODS: The study was a prospective cohort study. A total of 304 patients with paroxysmal AF were enrolled, including 66 who underwent radiofrequency ablation (RFA). Serum HMGB1 levels were measured using an enzyme-linked immunosorbent assay. The primary endpoint was the first occurrence of a major adverse cerebrovascular event (MACE), defined as an acute ischemic stroke or all-cause mortality. RESULTS: During the median follow-up of 81.5 months, 76 MACEs were recorded. Patients were categorized into MACE and no-MACE groups based on the occurrence of MACE. The MACE group showed significantly higher age, CHA(2)DS(2)-VASc scores, and serum HMGB1 levels than the non-MACE group (p<0.05). The areas under the curve (AUC) for HMGB1 and CHA(2)DS(2)-VASc were 0.779 [95% (confidence interval, CI): 0.728-0.824)] and 0.818 (95% CI: 0.770-0.860), respectively. The combination of HMGB1 and CHA(2)DS(2)-VASc yielded an AUC of 0.895 (95% CI: 0.855-0.927), which was significantly higher than that of either metric alone (P < 0.05). Kaplan-Meier analysis showed that patients with high HMGB1 levels had a significantly lower event-free survival rate for MACE than those with low HMGB1 levels (P < 0.05). Multivariate Cox regression analysis identified HMGB1 level [(Hazard ratio, HR), 4.161; 95% CI, 2.518-6.878)] as an independent predictor of MACE in paroxysmal AF, along with the CHA(2)DS(2)-VASc score (HR: 5.567, 95% CI: 3.089-10.032). CONCLUSION: Elevated serum HMGB1 level was identified as a significant predictor of stroke or mortality in patients with paroxysmal AF, and may enhance the predictive capacity of current risk stratification tools while supporting more personalized anticoagulation strategies.