Study Clarifies Effect of Drugs on Retinal Vessel Diameter in Type 1 Diabetes
By Roxanna Guilford-Blake 2010-02-11
Elsevier Global Medical News
发表在2月期《眼科学文献》（the Archives of Ophthalmology）上的一项多中心研究发现，无论依那普利还是氯沙坦均无法造成血压正常的正常蛋白尿1型糖尿病患者的视网膜血管直径的变化。此 外，基线血压较高亦似与视网膜平均动脉直径缩小无关。

Neither enalapril nor losartan were associated with changes in retinal vessel diameter in normotensive, normoalbuminuric individuals with type 1 diabetes mellitus. Moreover, higher baseline blood pressure did not appear to be associated with the narrowing of average retinal arteriole diameter, according to results of a multicenter study reported in the February issue of the Archives of Ophthalmology.

Investigators found no statistically significant effect on changes in average retinal arteriole (central retinal arteriole equivalent, or CRAE) and venule (central retinal venule equivalent, or CRVE) diameter with angiotensin-receptor-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) therapy compared with placebo, reported Dr. Ronald Klein of the University of Wisconsin, Madison, and colleagues in Minnesota and Canada.

Participants came from the Renin-Angiotensin System Study (RASS), a parallel, double-blind, placebo-controlled, multicenter clinical trial of primary prevention of diabetic nephropathy conducted in Minneapolis, Montreal, and Toronto. The 285 subjects were randomly assigned to one of three treatment groups: losartan potassium (an ARB), enalapril maleate (an ACEI), or placebo.

Researchers analyzed 147 participants (mean age of 31.3 years; 80 women) who had fundus photography before randomization and whose retinal vessels were measurable. Of these, 124 also had 5-year follow-up photographs that were “gradable for retinal vessel measurements.”

Retinal vessel diameters were measured at baseline and at 5-year follow-up examinations by a computer-assisted technique. Graders were blinded. The protocol included resting blood pressure and pulse rate measurements as well as 24-hour ambulatory BP and pulse monitoring at baseline and at follow-up, investigators said.

Controlling for age and other factors, Dr. Klein and his colleagues said they found that “none of the 5-year average BP variables was significantly associated with change in CRAE or CRVE.”

Moreover, despite their beneficial effect in reducing the progression of diabetic retinopathy, neither enalapril nor losartan had any statistically significant effect compared with placebo on changes in CRAE or CRVE, they reported (Arch. Ophthalmol. 2010;128:198-205).

“The lack of an effect on CRAE and CRVE in our study is not consistent with findings of earlier studies that showed that ACEI or ARB treatment either reduced the amount of narrowing or increased the width of retinal arterioles,” investigators said.

However, they advised caution in interpreting their findings, noting that factors associated with variability of measurements of CRAE and CRVE “may have limited the ability to find associations with retinal vessel measurements in this cohort.”

As previously reported for the RASS, treatment with enalapril and losartan did reduce the rate of 2-step or more progression of diabetic retinopathy by approximately 65% despite this lack of effect on CRAE and CRVE.

Dr. R. Klein is an advisory board member for DIRECT/AstraZeneca, Pfizer, Eli Lilly and Co., and Novartis. Other authors received fees and/or grants from Merck & Co., AstraZeneca, Boehringer Ingelheim, Pfizer, Organon, Wyeth, and Genzyme Corp.

This study was funded by Juvenile Diabetes Research, the National Institutes of Health, Merck & Co, Merck Frosst, and the Canadian Institutes of Health.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

发表在2月期《眼科学文献》（the Archives of Ophthalmology）上的一项多中心研究发现，无论依那普利还是氯沙坦均无法造成血压正常的正常蛋白尿1型糖尿病患者的视网膜血管直径的变化。此外，基线血压较高亦似与视网膜平均动脉直径缩小无关。

美国麦迪逊市威斯康星大学的Ronald Klein博士和明尼苏达及加拿大的同事报告：研究发现与安慰剂相比，血管紧张素受体转化酶抑制剂（ACEI）或血管紧张素阻滞剂（ARB）并未显著改变视网膜小动脉平均直径（相当于视网膜中央小动脉，或CRAE）和小静脉平均直径（视网膜中央小静脉当量，CRVE）。

受试者来自肾素-血管紧张素系统研究（RASS），这是一项在明尼阿波利斯、蒙特利尔和多伦多开展的针对糖尿病视网膜病初级预防的平行双盲安慰剂对照多中心临床研究。285例受试者被随机分配接受氯沙坦钾（一种ARB）、马来酸依那普利（一种ACEI）或安慰剂治疗。

研究者对147例在随机分配接受治疗之前进行过眼底摄影且视网膜血管可测的受试者进行了分析，其平均年龄为31.3岁，80例为女性。其中124例受试者接受了眼底摄影的5年随访，进而获得了“视网膜血管测量梯度”。

利用计算机辅助技术对基线视网膜血管直径进行测量，并对其进行5年的随访检测。梯度分级也采取盲法。研究者说，研究内容包括静息血压和脉搏、基线24h动态血压和脉搏监测及其随访。

Klein和其同事说：在排除了年龄及其他因素的影响后发现“无任一5年平均血压变量与CRAE或CRVE的变化显著相关”。

研究者报告：另外，虽然具有减缓糖尿病性视网膜病进展的功效，但与安慰剂相比，依那普利或氯沙坦并未显著改变CRAE或CRVE(Arch. Ophthalmol. 2010;128:198-205)。

研究者说：“本研究中依那普利或氯沙坦对CRAE和CRVE无效的结果与早期的研究不一致，之前的研究发现ACEI或ARB治疗可减轻视网膜小动脉狭窄或增大其直径。”

然而，研究者们表示应谨慎解读他们的研究结果，他们指出导致CRAE和CRVE测量变化的因素“可能限制了本研究发现视网膜血管测量相关性的能力”。

虽然对CRAE和CRVE无效，但之前RASS的报告显示，依那普利和氯沙坦确实降低了糖尿病视网膜病2级或更高进展率近65%。

R. Klein博士是DIRECT/阿斯利康、辉瑞、礼来和诺华公司的顾问委员会的成员。其他作者接受过默克、阿斯利康、勃林格殷格翰、辉瑞、欧加农、惠氏和Genzyme公司的酬金和（或）赠予。

该研究受到青少年糖尿病研究（Juvenile Diabetes Research）、国立卫生研究院（NIH）、默克公司、Merck Frosst公司和加拿大卫生研究院的资助。