降血脂藥物與視網膜血管阻塞疾病之研究

Lipid-lowering drugs and retinal vascular occlusion

陳豈㠆(Chi-Dan Chen)

指導教授 ： 季瑋珠

共同指導教授 ： 陳建煒

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201703390

摘要

網膜血管阻塞，俗稱眼中風，是一種嚴重影響視力的常見眼血管疾病。根據文獻，網膜血管阻塞被認為和高血脂和動脈粥狀硬化等心血管危險因子相關。近年來研究網膜血管阻塞所造成的臨床表現與預後文獻逐漸增加，在藥物介入預防網膜血管阻塞的探討仍十分缺乏，本研究為探討不同降血脂藥物的使用狀況與網膜血管阻塞的預防。

本病例對照研究利用全民健保資料庫全人口檔將2009-2013年中第一次發生網膜血管阻塞的40歲以上病患納入研究組，撈取定義為須有一年內非同日之兩次網膜血管阻塞門診或一次住院代碼者，其中若非眼科醫師所開立以及資料有缺失者皆被排除。對照組分為三組，第一組依照1:20比例進行頻率配對撈取出的健康對照組，並刪除40歲以下、性別年齡資料有缺失的對象；第二組將第一組對照組中完全沒有就醫資料者刪除；第三組則為依照1:3的比例進行年齡組別與性別的配對。以上三組對照組的配對日期(index date)皆為配對年(index year)中隨機挑選一日。藥物從配對日期往前回溯兩年的statin與fibrates累積用藥量，分別分析累積處方開立次數與累積用藥量對於眼中風之間的保護效果為何。

從結果得知年齡與男性對於網膜血管阻塞疾病為顯著相關的危險因子，特別是年齡介於60-69歲的族群為高風險族群；降血脂藥物雖在三組比較當中無全面明顯的保護效果，然而在simvastatin, rosuvastatin, fluvastatin這三種藥物的累積中高劑量當中，可看到對於網膜血管阻塞疾病有著顯著的保護效果。

本研究為第一篇詳細探討不同降血脂藥物與網膜血管阻塞疾病直接的保護關係，加上樣本數大以及資料具全國代表性，不會有嚴重的偏差；然而仍有許多限制，例如缺乏臨床資料、適應症干擾(confounding by indication)，以及無法得知實際用藥情況與藥物之間的交互作用關係。本篇研究可供未來欲往相關領域的研究者進行參考。

關鍵字

網膜血管阻塞 ； 降血脂藥物 ； 眼中風 ； statins ； 健保資料庫

並列摘要

Retinal vascular occlusion, also called "eye stroke", may cause severe visual loss. The most recognized risk factors are hyperlipidemia, atherosclerosis and cardiovascular disorders. Recently, an increasingly large number of literature focus on the clinical management and prognosis of retinal vascular occlusion. However, the research on primary prevention of retinal vascular occlusion still lacks. This study aims at studying the preventive association between lipid-lowering drugs and retinal vascular disease.

Data for this study were obtained from the Taiwan National Health Insurance (NHI) Claims Database. Subjects who had a first diagnosis for RVO with once hospitalization or with at least two outpatient claims within one year during 2009-2013 were identified as cases. The records confirmed by ophthalmologists were included. Control I were 1:20 frequency matched from the original population beneficiaries, control II were a subset group from control I, which further excluded patients who has no medical records in the database; and control III were from control II, 1:3 matched with age and gender with RVO case. All the three control groups contained patients aged older than 40 without any RVO history. The index date of each control was randomly assigned with a date within the study period, and all the participations without gender and birth information were excluded. Drug exposure was traced back for two years for summing the cumulative prescription and defined daily dose (DDD) of statins and fibrates.

We can infer from the analyzing results that aging and male gender are the significant risk factors for retinal vascular occlusion, especially in the age group 60-69. Furthermore, we found in the medium to high cumulative dose of simvastatin, rosuvastatin and fluvastatin were significant protective for retinal vascular disease.

This study is the first one to investigate the protective effect between the detailed lipid-lowering drugs and retinal vascular disease and we have large sample size in this study, which rarely results in serious biases. Nevertheless, there are still some limitations, such as lacking clinical sample (BMI, smoking status and drinking habits.), possible confounding by indication and we couldn’t acquire the truly medication usage of the subjects in our study as well as the drug-drug interactions need further investigations. This study can be references for the future related investigators.

並列關鍵字

Retinal vascular occlusion ； lipid-lowering drugs ； HMG-CoA reducatase inhibitors ； statins ； national health insurance claims database

參考文獻

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