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-inhibitors. No data are available showing a endothelial-protective effect by determining 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 months in diabetic patients. 87 patients with an urinary albumin concentration (UAC) below 100 mg/l at baseline were included 46 patients were treated without 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 blood glucose, blood pressure or diet. At study entry both groups were comparable with respect to duration of diabetes, diabetic complications, vascular risk factors, body mass index, medications used to treat diabetes, presence of hypertension, glycemic control, tryglycerides, HDL cholesterol, creatinine, UAC and plasma-TM. Age, blood pressure, and total cholesterol were significantly higher in the ACEI group, compared with the control group. Results: After a follow up of 18 months a significant increase in UAC (Delta UAC = 10.48 mg/l, p = 0.03) and plasma-TM (Delta TM = 3.06 ng/l, p = 0.009) was observed in the control group, while in the ACEI treated group a decrease in albuminuria (Delta UAC = -7.44 mg/l, p = 0.01) and plasma-TM (Delta TM = -4.78 ng/l, p 0.001) was seen. Despite a similar approach in hypertension and diabetes control in both groups, UAC and plasma-TM decreased after 18 months only in the ACEI treated group. Treatment with ACEI was the strongest predictor (p=0.0001) indicating decrease of UAC and plasma-TM (multi regression analysis). Conclusion: Plasma-thrombomodulin might be a useful marker for assessing the efficacy, of drugs potentially protecting the vessel wall. While the present study was a open, non randomized study, further investigation is necessary to proof the hypothesis in a randomized, placebo-controlled, double-blind study.