大剂量高效他汀类药物可降低痴呆风险

阿姆斯特丹——台湾一项回顾性观察研究结果显示，服用最高总等效剂量的高效他汀类药物(如阿托伐他汀或瑞舒伐他汀)可使老年患者痴呆风险降低75%。

台大医院新竹分院的Tin-Tse Lin博士在欧洲心脏病学会(ESC)年会上报告称，上述作用可能与他汀类降低胆固醇、抗血栓形成以及抗炎作用有关。但该研究显示，高剂量洛伐他汀(目前处方量较少)与痴呆发生呈正相关。

专家指出，上述结果为破解他汀类与痴呆难题提供了新的信息，并且可以减轻人们对所谓他汀类“脑雾”作用的担心。

韦恩州立大学心内科主任、美国心脏病学会(ACC)副会长Kim Williams Sr.博士称，令人欣慰的是，该研究没有发现痴呆与使用日益广泛的他汀类相关的真实证据，但洛伐他汀等老的他汀类药物仍令人担心。Williams博士没有参与该项研究。

2012年，美国食品药品管理局(FDA)在他汀类药物标签中添加一项警告，称该类药物可导致暂时记忆丧失和意识模糊。但与此同时，包括一项综述在内的多项研究表明，他汀类与认知损害并无因果关系或确切关联。


Tin-Tse Lin博士
 
在这项台湾研究中，研究者利用国民健康保险数据库中100万例随机样本，确认了1997~1998年期间年龄＞65岁且无痴呆史的近58,000例患者，并对他们平均随访4.5年。根据受试者平均每日等效剂量或总等效剂量(整个随访期间)，他们被分为三分位组：低、中和高剂量。主要终点为新确诊的早老性痴呆和老年性痴呆，并排除血管性痴呆患者。

随访期间，5,500余例患者被确诊为痴呆，其余52,000例患者作为对照组。

结果显示，校正后痴呆风险比与总的或每日等效剂量增加呈显著性负相关。对于不同年龄、性别和心血管风险亚组患者，他汀类的保护作用仍非常明显，统计学趋势显著。

Lin博士指出，目前尚不清楚上述结果是否可外推至其他种族人群。他推测，胆固醇代谢障碍可导致心血管疾病发病率增加，胆固醇水平提高还可导致与神经退行性病变相关的炎性程度增加，因此，他汀类降低痴呆风险有其合理性。

挪威奥斯陆大学的Terje R. Pedersen教授评论指出，“他汀类居然会影响阿尔茨海默病进展，这一现象令人难以置信，但似乎有道理的是，当你预防动脉粥样硬化进一步发展的同时，也可能预防了痴呆的发生。”

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By: NASEEM S. MILLER, Cardiology News Digital Network

AMSTERDAM – Elderly patients who received the highest total equivalent doses of high-potency statins, such as atorvastatin or rosuvastatin, had a threefold decrease in the risk of developing dementia, according to a retrospective, observational study in Taiwan.

Dr. Tin-Tse Lin, who presented the study at the annual congress of the European Society of Cardiology, said that the mechanism might be due to the statins’ effect on cholesterol reduction, antithrombotic activity, and their anti-inflammatory effect. The study, however, showed that lesser-prescribed lovastatin at a higher dose was positively associated with dementia development. 

The findings add another piece to the statin-dementia puzzle and may alleviate some of the concerns with the so-called "brain fog" effect of statins, experts said.

Dr. Kim Williams Sr., chair of cardiology at Wayne State University, Detroit, said that the study "was very reassuring in that there was no real evidence of dementia with the statins that we tend to use, which are the more powerful ones." Older statins like lovastatin, however, are still of concern, said Dr. Williams, vice president of the American College of Cardiology, who was not involved in the study.

In 2012, the Food and Drug Administration added a warning to the statins’ label that the drugs could cause temporary memory loss and confusion.  Meanwhile, several studies, including a 2012 review, have found no causality or conclusive relationship between statins and cognitive impairment. 

For the Taiwanese study, researchers used a random sample of 1,000,000 people covered by the country’s National Health Insurance. They identified nearly 58,000 patients who were older than 65 years of age and without a history of dementia in 1997 and 1998. The patients were followed up for an average of 4.5 years. 

The study was divided into tertiles – low, medium, and high dosage – according to mean daily equivalent or total (across the entire follow-up period) equivalent dosage. 

The primary endpoint was new diagnosis of presenile and senile dementia. Patients with vascular dementia were excluded. 

More than 5,500 developed dementia. The remaining 52,000 patient served as controls. 

Results showed that the adjusted hazard ratios for dementia were significantly inversely associated with increased total or daily equivalent statin dosage among the tertiles. For total equivalent statin dosage, the hazard ratios for dementia were 0.77 (low dosage), 0.63 (medium), and 0.33 (high), compared with controls, all significant differences. For mean equivalent daily dosage, HRs for dementia were 0.62, 0.70, 0.42, respectively, compared with controls, also significant differences. 

The authors said that the protective effect of statins remained robust in different age, gender, and cardiovascular risk subgroups, with strong statistical trends. 

Dr. Lin of the National Taiwan University Hospital, Hsin-Chu, Taiwan, said he did not know whether the findings would apply to other ethnicities. 

He hypothesized that because disorders of cholesterol metabolism could lead to an increased incidence of cerebrovascular disease, and elevation of the cholesterol level may result in a high inflammatory status associated with neurodegeneration, "I think it is reasonable to say that statins may facilitate lowering the risk of dementia."

Prof. Terje R. Pedersen of the University of Oslo (Norway), who commented on the study, said that "It is implausible that statins have any impact on progression of Alzheimer’s disease, but it might be plausible to think that when you prevent extensive atherosclerosis, then you also prevent dementia."