N2 – Coronary heart disease (CHD) is highly prevalent in patients with diabetes mellitus (DM), and remains the single most common cause of death among this population. In particular, we report here for the first time that FMD is independently associated with SMI; and even more specifically when ischemia is associated with CAD on angiography. Results Patients with longer duration of diabetes possessed higher rates of obstructive CAD (P < 0.001). Published for the Infectious Diseases Society of America. Significant stenosis was defined as coronary artery stenosis > 70%. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. Mean LVEF at rest and after exercise in the normal group was 66 +/- 7% and 76 +/- 9%, respectively. The coronary disease distribution was described based on the affected vessel: LCA, LAD artery, circumflex artery (CX), and right coronary (RCA) artery. The prevalence and severity of asymptomatic CAD are comparably high in men and women with T2DM. Prevalence was highest in the age group between 75 and 85 years and already 600,000 individuals between 30 and 70 years were known to have diabetes . MRI is more sensitive than X-ray to detect traumatic skeletal lesions . The organisms are not sensitive to the commonly available antibacterial agents. This is a high volume procedure laboratory serving as the hub in our district. All eligible patients will be asked to participate. A recent US report demonstrated that the mortality rates among both American men and women with diabetes decreased substantially between 1997 and 2006, reducing the absolute difference between adults with and without diabetes . At the first visit they will be given a brochure containing detailed information about diabetes, hypertension, atherosclerosis and prevention. All participants will continue with regular follow ups scheduled by the referral diabetes outpatients service. Personal and clinical data regarding diabetes, cardiovascular risk factors, medications and blood pressure measurements will be collected. Information on laboratory parameters including lipid profile, serum creatinine, HbA1c will also be collected. Cardiovascular risk will be calculated according to the Italian risk chart provided by Istituto Superiore di Sanità . During follow up the occurrence of any clinical event included in the end-points will be notified and verified through the registers of local Hospital admissions.
After the completion of follow each patient will be contacted for the final visit. We chose a stratified block randomization with one to one allocation ratio. Diabetes was diagnosed according to American Diabetes Association criteria (17). Pharmacological/behavioural prevention of cardiovascular events will be the same in both groups. Experimental and control group will continue to be followed at our local Diabetic Clinics that will try to provide maximal adherence the European Society of Cardiology Guideline  indications about control of hypertension, hypercholesterolemia and glycaemia. A maximal symptom-limited exercise protocol will be used with a treadmill (T-2100 Treadmill – GE Healthcare medical system) according to the standard Bruce protocol. Patients underwent 2D transthoracic echocardiography at baseline and at 2-year follow-up using a commercially available system (Vivid 7 and E9, General-Electric Vingmed, Horton, Norway) equipped with 3.5-MHz and M5S transducers.
Twelve ECG leads will be recorded every minute and blood pressure will be measured manually at rest and every three minutes. Ventilatory oxygen consumption, expressed in multiples of resting requirements (METS), will be estimated by exercise duration. The exercise test will be defined as maximal if the patient will reach 80% of the predicted exercise capacity according to Gulati formula . Sub maximal tests without ECG signs and/or symptoms of ischemia will be considered not diagnostic and will not lead to any other procedure. The exercise test will be considered positive if showing horizontal or downsloping ST segment depression of 1 mm or more calculated at 0.06-0.08 second after the J point at precordial leads (V3-V6). Coronary artery disease will be defined as being significant if lumen stenosis will be greater than 50% at level of left main or left anterior descending, or greater than 70% at level of circumflex or right coronary artery. Based on existing data we can assume that about 80% patients will test negative  and run a risk of 0.97% per year  while the remaining 20% of patients will test positive running a risk of 1.03% per year after treatment according to the results of the ACIP trial .
This results in a mean risk of 1.03 per year within the group. The cardiac event rate reported in over 10000 Italian diabetic patients without evidence of cardiac disease was collected by the Italian Istituto Superiore di Sanità (Diabetes and Informatics Study Group): the cumulative incidence of cardiac events was 2.88% per year in men and 2.33% per year in women . The incidence rates will be estimated using Kaplan-Meier survival curves that will be compared using logrank analysis. The treatment efficacy will be assessed by multivariate analyses using Cox’s regression model. During the study interim analyses will be performed every year with the scope of verifying the correctness of the assumptions made for sample size estimation with regard to the primary end point event rate (this information can influence the duration of follow up) and to avoid unforecast excess of event rate in the treatment group. We will assess the incremental costs and the economic consequences of screening for asymptomatic coronary artery disease in diabetic patients with the aim of revascularization compared with usual care alone according to established methods for the analysis of patient-level data . The association of diabetes mellitus and urinary tract infections is increasingly being reported.
The study will be conducted in accordance with European Commission guidelines for Good Clinical Practice and performed according to the revised Declaration of Helsinki. The study protocol was approved by local Ethical Committee. The trial was registered at ClinicalTrial: the U.S. National Institute of Health registry of federally and privately supported clinical trials conducted in the United States and around the world [NCT00547872]. The study results will be submitted for publication in an appropriate journal irrespective of the outcome. Trial data will be reported according to the Consolidated Standards of Reporting Trials (CONSORT statements) . The principal investigator will be responsible for timely generation of report manuscripts, and prior to submission the co-investigators will review and approve study results.