Wolozin Benjamin, Wang Stanley W, Li Nien-Chen, Lee Austin, Lee Todd A, Kazis Lewis E
Boston University School of Medicine, Boston, MA, USA.
BMC Med. 2007 Jul 19;5:20. doi: 10.1186/1741-7015-5-20.
Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.
We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.
We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects > or =65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700,000 subjects taking simvastatin and over 50,000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44-0.48, p < 0.0001) and 0.91 (CI 0.80-1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4-0.55, p < 0.0001).
Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.
他汀类药物是一类通过抑制3-羟基-3-甲基戊二酰辅酶A还原酶来降低胆固醇的药物。由于结果相互矛盾，他汀类药物是否能使痴呆患者获益仍不明确。我们推测，文献中的一些混淆可能源于不同他汀类药物疗效的差异。我们使用一个大型数据库来比较几种不同他汀类药物的作用，以研究某些他汀类药物是否与痴呆和帕金森病发病率的降低存在不同关联。
我们分析了美国退伍军人事务数据库决策支持系统中的数据，该数据库包含450万受试者的诊断、用药和人口统计学信息。在对与痴呆或帕金森病相关的协变量进行调整后，使用Cox比例风险模型，将服用他汀类药物的受试者与服用除他汀类药物外的心血管药物的受试者进行比较，研究洛伐他汀、辛伐他汀和阿托伐他汀与痴呆的关联。
我们观察到，使用三种模型中的任何一种，辛伐他汀都与65岁及以上受试者痴呆发病率的显著降低相关。第一个模型对年龄进行了调整，第二个模型对痴呆的三个已知风险因素（高血压、心血管疾病或糖尿病）进行了调整，第三个模型对Charlson指数进行了调整，该指数是一个对慢性病进行广泛评估的指标。获得了超过70万名服用辛伐他汀和超过5万名服用阿托伐他汀的64岁以上受试者的数据。使用模型3，辛伐他汀和阿托伐他汀新发痴呆的风险比分别为0.46（95%置信区间0.44 - 0.48，p < 0.0001）和0.91（95%置信区间0.80 - 1.02，p = 0.11）。洛伐他汀与痴呆发病率的降低无关。辛伐他汀对新患帕金森病的风险比也有所降低（风险比0.51，95%置信区间0.4 - 0.55，p < 0.0001）。
辛伐他汀与痴呆和帕金森病发病率的大幅降低相关，而阿托伐他汀与新发痴呆和帕金森病发病率的适度降低相关，仅显示出有显著意义的趋势。
