Sodium-glucose co-transporter2 expression and inflammatory activity in diabetic atherosclerotic plaques: Effects of sodium-glucose co-transporter2 inhibitor treatment

Objective: We evaluated sodium-glucose co-transporter2 (SGLT2) expression and the effect of SGLT2 inhibitor (SGLT2i) therapies on carotid plaques of asymptomatic diabetic and non-diabetic patients. Methods: Plaques were obtained from 296 non-diabetic patients and 227 patients with type 2 diabetes undergoing carotid endarterectomy. 97 patients with type 2 diabetes were treated with SGLT2 inhibitors for 16 +/- 4 months before endarterectomy. After propensity score matching analysis, patients with type 2 diabetes were categorized without (n = 87) and with SGLT2i therapy (n = 87). To investigate SGLT2 expression levels' effects on major adverse endpoints (MACE = stroke, transient ischemic attack, myocardial infarction, and death), we evaluated MACE outcomes at a 2-year follow-up. Results: Compared to plaques from patients without diabetes, plaques from patients with diabetes had higher SGLT2 expression, inflammation, and oxidative stress, along with lower SIRT6 expression and collagen content. Compared with plaques from patients with diabetes, SGLT2itreated patients with type 2 diabetes presented increased SIRT6 expression and collagen content and lowered inflammation and ion and oxidative stress, thus indicating a more stable plaque phenotype. These results supported in vitro observations on human aorta endothelial cells (EC) (TeloHAEC-cells). Indeed, EC treated with high glucose (25 mM) in the presence of SGLT2i (100 nM canagliflozin) presented higher SIRT6 expression and decreased mRNA and protein SGLT2 levels, nuclear factor-kappa B (NF-B(NF - KB), and matrix metallopeptidase 9 (MMP-9) expression compared to cells treated only with high glucose. After two years following endarterectomy, a multivariable Cox regression analysis showed significantly higher 2-year overall survival from MACE in patients without diabetes (P < 0.01). Among patient with diabetes, the current SGLT2i users presented a significantly lower rate of MACE through 2 years compared to non-SGLT2i users (P < 0.05). Conclusions: These findings unveil a critical involvement of the SGLT2/SIRT6 pathway in the inflammatory process of diabetic atherosclerotic lesions and suggest its possible favorable modulation by SGLT2i. (c) 2021 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Coronary angioplasty with stenting for acute coronary syndrome in patients with isolated single coronary artery: a report of two cases.

In the largest reported series of patients, the overall angiographical incidence of congenital coronary anomalies was 1.3%. Among these anomalies, an isolated single coronary artery is a rare, congenital coronary anomaly with an incidence of 0.044-0.23%. In this kind of anomaly, the coronary arteries arise by a single coronary ostium in the right or left sinus of Valsalva. Percutaneous coronary revascularization plays an important role in the management of acute coronary syndrome, and coronary anomalies may determine a lower success rate of this intervention. We report two cases of isolated single coronary arteries who underwent successful coronary angioplasty and stenting for acute coronary syndrome

Acute aortic syndromes at high surgical risk: the endovascular approach.

Aims: Acute aortic syndromes (AAS) still represent life-threatening conditions. The aim of this study was to describe our experience in the management of patients (pts) with AAS and to evaluate the safety and feasibility of endovascular treatment (EVT) in high surgical risk patients. Methods and results: One hundred and four patients underwent EVT. We selected 56 pts with AAS: 17 complicated type B aortic dissections, five traumatic aortic ruptures at the isthmus, 11 thoracic aneurysms and 23 pts with large AAA with impending rupture. All these pts were at high surgical risk because of their comorbidities and/or their emergency situation. They were clinically followed during hospitalisation and they underwent a 2 mm-interval CT-scan two weeks, six and 12 months after discharge and every year after. Death, paraplegia, open surgical conversion did not occur. Two pts underwent a successful secondary EVT for type I endoleak. One patient with thoracic aortic aneurysm died of septic shock from pneumonia 78 days after discharge and two pts with AAA suffering from a severe three-vessel coronary disease experienced sudden death at one year follow-up. Conclusions: EVT seems to be a safe and effective therapeutic option with good short- and midterm results in patients with AAS at high surgical risk. Thus, it can be considered as a less-invasive alternative in patients considered otherwise unsuitable for conventional surgery, even though a careful, continued follow-up is still necessary to confirm the long-term safety and effectiveness of EVT in AAS

Abciximab in elderly with acute coronary syndrome invasively treated: effect on outcome.

Older age is an independent predictor of mortality after percutaneous coronary intervention (PCI) in patients with Non-ST elevation Acute Coronary Syndrome (ACS). GPIIb/IIIa inhibitors are proved to improve outcome in high risk patients, but conflicting data are available about the effects of these inhibitors in elderly. Accordingly, we studied a consecutive population of elderly patients undergoing PCI for Non-ST elevation ACS. A total of 500 patients were divided in: GPI group (247 pts; mean age 77+/-1.9 years) treated by stenting plus abciximab and, no GPI group (253 pts; mean age 77+/-2.4 years) treated by stenting alone. Propensity analysis was used to account for the nonrandomized use of GPIIb/IIIa inhibitors. During hospitalization, incidence of death was similar among groups (3.2% vs 4.6%) without difference regarding incidence of major (1.6% vs 1.1%) and minor bleedings (4% vs 3%). At long-term follow-up the rate of death was significantly lower in GPI group (4.5% vs 12.3%; p=0.002) as well as the rate of acute myocardial infarction (2.8% vs 11.1%; p=0.0001), and pre-PCI (5.7% vs 13.4%; p=0.003). Cox regression analysis identified abciximab use as an independent predictor of lower long-term major adverse cardiac event (MACE) after adjustment for propensity score (Exp (B) 0.620, 95%CI 0.394-0.976, p=0.039). Our results suggest that addition of abciximab to stenting improves outcome in elderly patients with Non-ST elevation ACS, leading to an absolute benefit for reduction of death and MACE, with an acceptable rate of major and minor bleeding

Abciximab in elderly with acute coronary syndrome invasively treated: effect on outcome.

Older age is an independent predictor of mortality after percutaneous coronary intervention (PCI) in patients with Non-ST elevation Acute Coronary Syndrome (ACS). GPIIb/IIIa inhibitors are proved to improve outcome in high risk patients, but conflicting data are available about the effects of these inhibitors in elderly. Accordingly, we studied a consecutive population of elderly patients undergoing PCI for Non-ST elevation ACS. A total of 500 patients were divided in: GPI group (247 pts; mean age 77+/-1.9 years) treated by stenting plus abciximab and, no GPI group (253 pts; mean age 77+/-2.4 years) treated by stenting alone. Propensity analysis was used to account for the nonrandomized use of GPIIb/IIIa inhibitors. During hospitalization, incidence of death was similar among groups (3.2% vs 4.6%) without difference regarding incidence of major (1.6% vs 1.1%) and minor bleedings (4% vs 3%). At long-term follow-up the rate of death was significantly lower in GPI group (4.5% vs 12.3%; p=0.002) as well as the rate of acute myocardial infarction (2.8% vs 11.1%; p=0.0001), and pre-PCI (5.7% vs 13.4%; p=0.003). Cox regression analysis identified abciximab use as an independent predictor of lower long-term major adverse cardiac event (MACE) after adjustment for propensity score (Exp (B) 0.620, 95%CI 0.394-0.976, p=0.039). Our results suggest that addition of abciximab to stenting improves outcome in elderly patients with Non-ST elevation ACS, leading to an absolute benefit for reduction of death and MACE, with an acceptable rate of major and minor bleedings

Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: The prospective AIRE Study

Additional file 1: Figure S1. Definition of the best cut-off level of ROC curves respectively for adiponectin (a), resistin (b) and TNF-alpha (c), according to the risk of restenosis. (Central panel) Definition of the best cut-off level of ROC curves respectively for adiponectin (a), resistin (b) and TNF-alpha (c), according to the risk of new stenosis. (Lower panel) Definition of the best cut-off level of ROC curves respectively for adiponectin (a), resistin (b) and TNF-alpha (c), according to the risk of any coronary event