Influence of ramipril on the course of plasma thrombomodulin in patients with diabetes mellitus

Background: In diabetic patients endothelial dysfunction is reflected by an increased urinary albumine excretion, which can be reduced by ACE-inhibito rs. No data are available showing a endothelial-protective effect by determ ining a marker reflecting endothelial cell-damage. Patients and methods: The effect of angiotensin converting enzyme inhibitor (ACEI) (ramipril) treatment on the progression of endothelial cell damage, assessed by measurement of plasma-thrombomodulin (TM), - was investigated in an open, non randomized prospective pilot study over a period of 18 mont hs in diabetic patients. 87 patients with an urinary albumin concentration (UAC) below 100 mg/l at baseline were included 46 patients were treated wit hout ACEI and sewed as a control group, 41 patients were treated with ACEI. Participation in this study did not affect intensity in the treatment of b lood glucose, blood pressure or diet. At study entry both groups were compa rable with respect to duration of diabetes, diabetic complications, vascula r risk factors, body mass index, medications used to treat diabetes, presen ce of hypertension, glycemic control, tryglycerides, HDL cholesterol, creat inine, UAC and plasma-TM. Age, blood pressure, and total cholesterol were s ignificantly higher in the ACEI group, compared with the control group. Results: After a follow up of 18 months a significant increase in UAC (Delt a UAC = 10.48 mg/l, p = 0.03) and plasma-TM (Delta TM = 3.06 ng/l, p = 0.00 9) was observed in the control group, while in the ACEI treated group a dec rease in albuminuria (Delta UAC = -7.44 mg/l, p = 0.01) and plasma-TM (Delt a TM = -4.78 ng/l, p 0.001) was seen. Despite a similar approach in hyperte nsion and diabetes control in both groups, UAC and plasma-TM decreased afte r 18 months only in the ACEI treated group. Treatment with ACEI was the str ongest predictor (p=0.0001) indicating decrease of UAC and plasma-TM (multi regression analysis). Conclusion: Plasma-thrombomodulin might be a useful marker for assessing th e efficacy, of drugs potentially protecting the vessel wall. While the pres ent study was a open, non randomized study, further investigation is necess ary to proof the hypothesis in a randomized, placebo-controlled, double-bli nd study.