Sortilin levels are associated with peripheral arterial disease in type 2 diabetic subjects

et al. 2020

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Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline level of Sortilin levels, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin serum levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, Sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between Sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using Sortilin levels the prediction of MACE incidence improved [area under the curve (AUC) = 0.94] and MALE (AUC = 0.72).Conclusions: This study demonstrates that Sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 58%

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Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

et al. 2020

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“…Starting from these biological supports, a detrimental role of sortilin for diabetic patient has been previously con rmed [20,31]. Furthermore, sortilin levels correlate with the presence of PAD and PAD severity in a cohort of diabetic patients [21]. Here we found that sortilin levels at baseline are higher in patients with lower ABI.…”

Section: Discussionsupporting

confidence: 61%

Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

et al. 2020

Preprint

Self Cite

Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72).Conclusions: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

“…Despite similar baseline clinical characteristics-in terms of risk factor control and PAD severity-and the same endovascular approach, some patients do not encounter complications for years while other patients may have complications, even fatal, within a few months [26]. Several potential biomarkers have been proposed, some linked to patient's genetic characteristics [25,[27][28][29], many linked metabolic and in ammatory parameters [19,25,[30][31][32][33]. Among the possible candidates, the pathways linked to adipose tissue represent a promising eld of study.…”

Section: Discussionmentioning

confidence: 99%

Association between Omentin-1 and Major Cardiovascular Events After Lower Extremity Endovascular Revascularization in Diabetic Patients: A Prospective Cohort Study

et al. 2020

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Background: Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients. In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE). Among adipokines, Omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity.Objective: To study the relationship between Omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization. Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months.Results: Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 ng/mL vs 30.82 ± 5.48 ng/mL, p < 0.001). Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up. We observed that Omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 ng/mL vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 ng/mL vs 31.34 ± 5.54 ng/mL, p < 0.001). The association between Omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis. Receiver operating characteristics (ROC) curve using Omentin-1 levels predicted incidence events (area under the curve = 0.80).Conclusions: We demonstrated that reduced Omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure.