Prevention of Cardiac and Vascular Events in Patients With NGT/IGT.

Overview

Impaired glucose tolerance or mild glucose elevations in the non-diabetic range are associated with increased cardiovascular disease and recent studies suggested the need to detect these glucose abnormalities early in the post-infarction period. Although in the last ten years procedures of coronary revascularisation have dramatically improved the outcome of non diabetic patients affected by ischemic heart disease, these procedures are less effective in patients with type 2 diabetes mellitus and IGT. Possible causes of worse prognosis in these patients could be related to the presence of hyperinsulinemia and insulin resistance due to the well known effect of insulin to increase neointimal tissue proliferation and in-stent restenosis, by stimulating vascular smooth muscle cell growth factors and migration. In addition, it is well known that endothelial dysfunction is an early functional disturbance in the development of atherosclerotic lesions. The impairment of eNOS action might change the turnover rate of eNOS or nitric oxide production and action influencing nitric oxide signalling, apoptosis cascade and angiogenesis. All these factors can contribute to endothelial dysfunction to a certain extent, and accelerate atherosclerosis with increased risk for cardiovascular disease. The constitutively expressed eNOS, is likely to be the major contributors to whole-body nitric oxide production. It is interesting to note that a region of chromosome 7q seems to influence both insulin resistance and blood pressure, suggesting that this locus may broadly influence traits associated with insulin resistance. L-arginine is an essential amino acid and its availability is important for the normal endothelial cell function and its intracellular reduction may contribute to the dysfunctional endothelial state. It is well known that L-arginine is as a precursor for nitric oxide and both in vitro and in vivo studies have demonstrated that L-arginine can augment vascular dilation under certain conditions. Our hypothesis is to evaluate the modulating effect of L-arginine on metabolic, endothelial variables and on myocardial function in patients with cardiovascular disease.

Condition: Patients submitted to coronary revascularization characterized for glucose tolerance after OGTT Intervention: L-arginine for 6 months Inclusion criteria: patients in stable clinical conditions after coronary revascularization (CABG and percutaneous angioplasty with/without stent implantation). Age \> 30 years, male and female. Fasting glucose levels below 126 mg/dl. Exclusion criteria. Type 1 diabetes mellitus, known type 2 diabetes mellitus, pregnancy, impaired kidney and liver function, severe and not treated arterial hypertension. Study type: randomized, double blind, Placebo, parallel