Borcea V, Morcos M, Isermann B, Henkels M, Ziegler S, Zumbach M, Amiral J, Längst K D, Seiz W, Ziegler R, Wahl P, Nawroth P P
Department of Internal Medicine I, University of Heidelberg, Germany.
Vasa. 1999 Aug;28(3):172-80. doi: 10.1024/0301-1526.28.3.172.
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.
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 served 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.
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).
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.
在糖尿病患者中，内皮功能障碍表现为尿白蛋白排泄增加，而血管紧张素转换酶抑制剂（ACEI）可降低这种排泄。目前尚无数据表明通过测定反映内皮细胞损伤的标志物能显示出内皮保护作用。
在一项为期18个月的开放性、非随机、前瞻性试点研究中，对糖尿病患者应用血管紧张素转换酶抑制剂（ACEI）（雷米普利）治疗对内皮细胞损伤进展的影响进行了研究，内皮细胞损伤进展通过测定血浆血栓调节蛋白（TM）来评估。纳入了87例基线时尿白蛋白浓度（UAC）低于100mg/l的患者。46例患者未接受ACEI治疗作为对照组，41例患者接受ACEI治疗。参与本研究不影响血糖、血压或饮食的治疗强度。研究开始时，两组在糖尿病病程、糖尿病并发症、血管危险因素、体重指数、用于治疗糖尿病的药物、高血压的存在、血糖控制、甘油三酯、高密度脂蛋白胆固醇、肌酐、UAC和血浆TM方面具有可比性。与对照组相比，ACEI组的年龄、血压和总胆固醇显著更高。
随访18个月后，对照组的UAC（ΔUAC = 10.48mg/l，p = 0.03）和血浆TM（ΔTM = 3.06ng/l，p = 0.009）显著增加，而在接受ACEI治疗的组中，蛋白尿（ΔUAC = -7.44mg/l，p = 0.01）和血浆TM（ΔTM = -4.78ng/l，p = 0.001）减少。尽管两组在高血压和糖尿病控制方面采用了相似的方法，但仅在接受ACEI治疗的组中，18个月后UAC和血浆TM下降。ACEI治疗是表明UAC和血浆TM下降的最强预测因素（p = 0.0001）（多元回归分析）。
血浆血栓调节蛋白可能是评估潜在保护血管壁药物疗效的有用标志物。虽然本研究是一项开放性、非随机研究，但有必要在随机、安慰剂对照、双盲研究中进一步验证该假设。
