他汀类药物应用与帕金森病发病关系的系统评价与Meta分析

发布时间：2018-08-21 10:17

【摘要】：背景和目的：帕金森病是一种常见的神经系统变性疾病,严重影响中老年人的健康及生活质量。随着我国人口老龄化的加剧,帕金森病的发病率逐年快速攀升。目前研究发现帕金森病发病与多种因素相关,其中他汀类药物可能具有降低帕金森病发病的作用。本文通过系统评价的方法探讨他汀类药物应用与帕金森病发病风险之间的关系。方法：计算机检索MEDLINE、Pubmed、EMbase、Scopus、the Cochrane Library、中国学术期刊全文数据库、维普数据库、万方数据库,并辅以人工检索,查找关于他汀与帕金森病发病关系的病例对照研究和队列研究,检索日期至2015年6月30日。按照纳入及排除标准进行文献筛选后,提取相关资料。应用纽卡斯-渥太华量表(Newcastle-Ottawa Scale, NOS)评价纳入研究的方法学质量后,采用Stata 14.0软件进行Meta分析。当纳入研究具有同质性或存在低度异质性时采用固定效应模型合并分析；当存在中度异质性时,采用随机效应模型(D-L法)合并分析；如果存在高度异质性,则不再进行Meta分析,仅进行描述性分析。采用Begg's检验、Egger's检验及漏斗图法进行发表偏倚的评估。采用敏感性分析检验结果的稳定性。进行亚组分析探讨异质性来源。分别合并不同种类他汀的效应量以探讨不同种类他汀间的疗效差异。对长期应用他汀的研究数据进行合并以探讨长期应用他汀类药物与帕金森病发病之间的关系。结果：共纳入11项研究,其中帕金森病患者21011例。纳入研究的NOS评分最高为9分,最低为6分,其中7项为高质量研究,4项为中等质量研究。异质性检验显示各研究间存在中度异质性(Cochrane's Q值=28.18,P=0.002；I2=64.5%),故采用随机效应模型进行合并分析。Meta分析结果显示：他汀应用者帕金森病发病率低于未应用者(RR=0.81,95%CI:0.71-0.92),差异有统计学意义(P=0.002)。敏感性分析证实了结果的稳定性。按研究设计类型、是否校正混杂因素、研究质量分组的亚组分析未改变上述结果。按研究地区分组的亚组分析显示：北美洲亚组：他汀应用者帕金森病发病风险与未应用者间的差异无统计学意义(RR=0.76,95%CI:0.54-1.08,P=0.128)；欧洲亚组：他汀应用者帕金森病发病率低于未应用者(RR=0.86,95%CI:0.80-0.93),差异有统计学意义(P=0.000)；亚洲亚组：他汀应用者帕金森病发病率低于未应用者(RR=0.73,95%CI:0.60-0.88),差异有统计学意义(P=0.001)。不同种类他汀间存在差异,阿托伐他汀、洛伐他汀、辛伐他汀、瑞舒伐他汀可降低帕金森病的发病率(RR=0.83,95%CI:0.66-1.05;RR=0.61,95%CI:0.16.2.35;RR=0.68,95%CI: 0.45-1.01;RR=0.88,95%CI:0.52-1.48),而普伐他汀可升高其发病率(RR=1.35, 95%CI:0.58-3.10),但上述结果均无统计学显著性。合并分析结果显示长期使用他汀类药物者与未使用者的帕金森病发病风险间的差异无统计学意义(RR=0.77,95%CI:0.56-1.07,P=0.120)。结论：他汀类药物应用可降低帕金森病发病风险。不同种类他汀与帕金森病发病风险的关系尚不明确,且目前证据尚不足以证明长期应用他汀可降低帕金森病发病风险。但上述结论需更多高水平队列研究及随机对照研究进一步验证。
[Abstract]:BACKGROUND AND OBJECTIVE: Parkinson's disease (PD) is a common neurodegenerative disease, which seriously affects the health and quality of life of middle-aged and elderly people. With the aging of the population in China, the incidence of Parkinson's disease is increasing rapidly year by year. Methods: MEDLINE, Pubmed, EMbase, Scopus, the Cochrane Library, Chinese Academic Journal Full Text Database, Wipper Database, Wanfang Database were searched by computer, supplemented by manual search. A case-control study and cohort study on the relationship between statins and Parkinson's disease were conducted from June 30, 2015. Literature was screened according to inclusion and exclusion criteria, and relevant data were extracted. The methodological quality of the included study was evaluated with the Newcastle-Ottawa Scale (NOS) and Stata 14.0 software was used. Meta-analysis was carried out. Fixed-effect models were used for merger analysis when homogeneity or low heterogeneity was included; random-effect models (D-L) were used for merger analysis when moderate heterogeneity was present; and meta-analysis was no longer performed if high heterogeneity was present; descriptive analysis was used only. Begg's test and Egger's test were used. Subgroup analysis was performed to explore the sources of heterogeneity. Effects of different types of statins were combined to explore the differences in efficacy between different types of statins. Data from long-term statins studies were combined to explore the long-term use of statins. Results: A total of 11 studies were included, including 21011 patients with Parkinson's disease. The highest NOS score was 9 and the lowest was 6, of which 7 were of high quality and 4 were of medium quality. Meta-analysis showed that the incidence of Parkinson's disease in statin users was lower than that in non-statin users (RR = 0.81, 95% CI: 0.71-0.92), and the difference was statistically significant (P = 0.002). Sensitivity analysis confirmed the stability of the results. Subgroup analysis showed that there was no significant difference in the risk of Parkinson's disease between statins users and non-statins in North America (RR = 0.76, 95% CI: 0.54-1.08, P = 0.128); and in Europe (RR = 0.8) the incidence of Parkinson's disease was lower in statins users than in non-statins (RR = 0.76, 95% CI: 0.54-1.08, P = 0.128). The incidence of Parkinson's disease was lower in statins users than in non-statins (RR = 0.73, 95% CI: 0.60-0.88), and the difference was statistically significant (P = 0.001). Incidence (RR = 0.83, 95% CI: 0.66-1.05; RR = 0.61, 95% CI: 0.16.2.35; RR = 0.68, 95% CI: 0.45-1.01; RR = 0.88, 95% CI: 0.52-1.48) and pravastatin increased the incidence (RR = 1.35, 95% CI: 0.58-3.10) of Parkinson's disease, but none of the above results were statistically significant. There was no significant difference in the risk of Parkinson's disease (RR = 0.77, 95% CI: 0.56-1.07, P = 0.120). Conclusion: Statins can reduce the risk of Parkinson's disease. Conclusion more high level cohort studies and randomized controlled trials are needed for further validation.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R742.5

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