Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population
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Maria Margherita Rando1, Federico Biscetti2, Andrea Leonardo Cecchini3
1Cardiovascular Internal Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.
Insights
High mobility group box-1 (HMGB-1) in diabetic patients with peripheral arterial disease predicts adverse cardiovascular and limb events after lower-extremity revascularization. Elevated HMGB-1 levels indicate a higher risk for these major adverse events.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Inflammation Research
Background:
- Peripheral arterial disease (PAD) is a serious complication of type 2 diabetes, increasing cardiovascular and limb event risks.
- High mobility group box-1 (HMGB-1) is a pro-inflammatory cytokine implicated in PAD among diabetic patients.
Purpose of the Study:
- To investigate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE).
- To assess HMGB-1 as a predictor of MACE and MALE following lower-extremity endovascular revascularization (LER) in diabetic patients with chronic limb-threatening ischemia (CLTI).
Main Methods:
- A prospective observational study included 201 diabetic patients with PAD and CLTI undergoing LER.
- Baseline serum HMGB-1 levels were measured before LER, with outcomes tracked over a 12-month follow-up period.
Main Results:
- Patients developing MACE or MALE had significantly higher baseline HMGB-1 levels (7.5 ng/mL vs. 4.9 ng/mL for MACE; 7.2 ng/mL vs. 4.8 ng/mL for MALE).
- Serum HMGB-1 remained a significant predictor of MACE and MALE after adjusting for cardiovascular risk factors.
- Receiver operating characteristic (ROC) analysis showed HMGB-1 effectively predicted MACE (AUC=0.78) and MALE (AUC=0.75).
Conclusions:
- Serum HMGB-1 levels are significantly associated with the occurrence of MACE and MALE post-LER in diabetic patients with PAD and CLTI.
- HMGB-1 may serve as a valuable biomarker for predicting adverse cardiovascular and limb outcomes in this high-risk population.
Background:
Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI).
Methods:
We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up.
Results:
During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75).
Conclusions:
This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.
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