Introduction: The nuclear protein high-mobility group box 1 (HMGB1), a potent factor for the innate host defense and/or tissue repair, has been suggested to be involved in the pathogenesis of several vascular diseases, including peripheral artery disease. However, it remains unclear whether serial measurements of serum HMGB1 levels may serve as a predictive markers for prognosis in critical limb ischemia (CLI) patients treated with endovascular therapy (EVT).
Hypothesis: A decrased HMGB1 levels after successful EVT is associated with good clinical outcome in patiets with CLI.
Methods: Plasma HMGB1 levels were measured immediately before EVT (baseline) and at 1, 3, 7 and 14 days after successful EVT in 117 CLI patients. Primary endpoint was amputation-free survival (AFS), defined as freedom from major amputation or death. 80 healthy individuals seved as control subjects.
Results: After 12 months of follow-up, 31 (26.5%) patients died and 14 patients (12.0%) received major amputation. Overall, baseline HMGB1 levels were higher in CLI patients than in healthy control subjects (6.87 ± 2.58 vs. 0.57 ± 0.32 ng/mL, P <0.001). When comparing the serial HMGB1 levels between patients with or without AFS, no intergroup differences in HMGB1 levels at baseline, 1, 3, and 7 days after successful EVT were found; however, the 14-day HMGB1 levels were significantly lower in AFS patients than in those without (3.18 ± 1.07 vs. 7.93 ± 2.84 ng/mL, P <0.01). A decreased 14-day HMGB1 level was an independent and significant predictor of long-term AFS (hazard ratio = 2.45; 95% confidence intervals, 1.33-5.78; p = 0.012).
Conclusions: Our results suggest that serial changes in plasma HMGB1 levels may serve as a predictive marker for AFS in patients with CLI after successful EVT.