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.
Rando, Maria Margherita; Biscetti, Federico; Cecchini, Andrea Leonardo; Nardella, Elisabetta; Nicolazzi, Maria Anna; Angelini, Flavia; Iezzi, Roberto; Eraso, Luis H.; DiMuzio, Paul J; Pitocco, Dario; Gasbarrini, Antonio; Massetti, Massimo; and Flex, Andrea, "Serum High Mobility Group Box-1 Levels Associated With Cardiovascular Events After Lower Extremity Revascularization: A Prospective Study of a Diabetic Population" (2022). Department of Surgery Faculty Papers. Paper 229.
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