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Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease.We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events.We performed a mean follow-up of 56 months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors.C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker.

The O subfamily of forkhead (FoxO) 1 is a pivotal element in the regulation of endothelial activation. Compartmentalization and activity of FoxO1 is regulated by post translational modifications, but the implication in endothelial dysfunction and atherosclerosis remain controversial. Our aim was to identify FoxO1 related metabolic signatures in endothelial cells.Using metabolomics in human umbilical endothelial cells (HUVECs) overexpressing the wild type FoxO1 (FoxO1-WT), the acetylation defective mutant (FoxO1-KR), the unphosphorylated nuclear localized mutant (FoxO1-ADA) and the Green Fluorescent Protein (GFP) control vector, we identify metabolic pathways differentially affected by the different FoxO1 localization and activity. Among metabolites, asymmetric dimethylarginine (ADMA) was increased in FoxO1-ADA compared with FoxO1-WT and FoxO1-KR infected cells (p0.01). ADMA was further investigated to identify the molecular mechanisms to explain its link to FoxO1. We found that unrestrained FoxO1 activity leads to increase of ADMA via downregulation of its degrading enzyme, dimethylaminohydrolase (DDAH) 1. In human subjects (n = 89) the FoxO1/DDAH1/ADMA pathway marks unstable atherosclerosis.Our results point to ADMA as a biomarker to track deregulated FoxO1 activity in vivo.

The chimney graft technique is gaining popularity as an alternative endovascular treatment for juxtarenal aneurysms not suitable for standard or fenestrated endovascular aneurysm repair (EVAR).1–6 Despite excellent technical success,1,3–6 limited data are available regarding the long-term effectiveness of the technique, particularly in terms of chimney stent occlusion. This complication may have catastrophic consequences and represents a challenge for any endovascular approach, requiring in most the cases an open surgical bypass to restore vessel patency. Donas et al.1 used open thrombectomy to treat a renal chimney graft thrombosis. We encountered a symptomatic acute thrombosis of a renal chimney stent-graft, which we successfully treated with endovascular thrombectomy using a recanalization device that, in a recent article in the JEVT, proved useful in treating acute popliteal thrombosis.7