Evaluation of sirtuin 1 as a predictor of cardiovascular outcomes in diabetic patients with limb-threatening ischemia

Abstract

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.

Keywords: Diabetes mellitus; Peripheral artery disease (PAD); Sirtuin 1.

Fig. 1

The freedom from MALE according to the cutoff of Sirtuin 1 was estimated using the Kaplan–Meier method and compared using the log-rank test (P < 0.01). The two groups of Sirtuin 1 are listed in the pattern code. The dashed line represents a Sirtuin 1 concentration > 3.79 ng/mL, and the solid line represents a Sirtuin 1 concentration < 3.79 ng/mL.

Fig. 2

Receiver operating characteristic (ROC) curves comparing the performance of a model without (Model 1) and with (Model 2) Sirtuin 1 levels in predicting major adverse limb events (MALE). The true-positive rate (sensitivity) is plotted as a function of the false-positive rate (1 - specificity). p < 0.01.