Rozani Violetta, Giladi Nir, El-Ad Baruch, Gurevich Tanya, Tsamir Judith, Hemo Beatriz, Peretz Chava
Department of Epidemiology, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Neurological Institute, Tel Aviv Medical Center, Tel Aviv, Israel.
PLoS One. 2017 Apr 7;12(4):e0175054. doi: 10.1371/journal.pone.0175054. eCollection 2017.
While experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson's disease (PD).
To evaluate the association between changes in statin adherence over time and PD risk.
A population-based cohort of new statin users (ages 40-79, years 1999-2012) was derived from a large Israeli healthcare services organization. Data included history of statin purchases and low density lipoprotein cholesterol (LDL-C) levels. Personal statin adherence was measured annually by the proportion of days covered (PDC). PD was detected employing a drug-tracer approach. Stratified (by sex, LDL-C levels at baseline and age) Cox proportional hazards models with time-dependent covariates were used to compute adjusted Hazard Ratio (HR) with 95%CI.
The cohort included 232,877 individuals, 49.3% men. Mean age at first statin purchase was 56.5 (±9.8) years for men and 58.7 (±9.2) years for women. PDC distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively. During a mean follow up of 7.6 (±3.4) years, 2,550 (1.1%) PD cases were identified. In a 1-year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency. Age-pooled HR (95%CI) for men and women with LDL-C levels at baseline ≤160mg/dL were: 0.99 (0.99-1.01), 1.01 (1.00-1.02); and for men and women with LDL-C >160mg/dL levels: 0.99 (0.98-1.01), 0.97 (0.98-1.01).
Our findings suggest that statin adherence over time does not affect PD risk. Future studies should use large-scale cohorts and refining assessments of long-term profiles in statin adherence.
虽然实验数据提供了一些令人信服的证据，证明他汀类药物对多巴胺能神经元有益，但观察性研究报告了关于他汀类药物影响帕金森病（PD）风险的潜力的相互矛盾的结果。
评估他汀类药物依从性随时间的变化与PD风险之间的关联。
基于人群的新他汀类药物使用者队列（年龄40 - 79岁，1999 - 2012年）来自以色列一个大型医疗服务组织。数据包括他汀类药物购买史和低密度脂蛋白胆固醇（LDL-C）水平。个人他汀类药物依从性每年通过覆盖天数比例（PDC）来衡量。采用药物追踪方法检测PD。使用具有时间依赖性协变量的分层（按性别、基线时的LDL-C水平和年龄）Cox比例风险模型来计算调整后的风险比（HR）及95%置信区间（CI）。
该队列包括232,877人，男性占49.3%。男性首次购买他汀类药物时的平均年龄为56.5（±9.8）岁，女性为58.7（±9.2）岁。整个随访期间男性和女性的PDC分布不同：中位数分别为58.3%和54.1%。在平均7.6（±3.4）年的随访期间，确定了2550例（1.1%）PD病例。在1年滞后分析中，我们发现无论他汀类药物类型和效力如何，所有年龄组中每年的他汀类药物依从性与PD风险之间均无关联。基线时LDL-C水平≤160mg/dL的男性和女性的年龄合并HR（95%CI）分别为：0.99（0.99 - 1.01），1.01（1.00 - 1.02）；基线时LDL-C >160mg/dL水平的男性和女性的年龄合并HR（95%CI）分别为：0.99（0.98 - 1.01），0.97（0.98 - 1.01）。
我们的研究结果表明，随时间推移的他汀类药物依从性不会影响PD风险。未来的研究应使用大规模队列，并改进对他汀类药物依从性长期概况的评估。
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