Discontinuation of statin therapy associates with Parkinson disease: A population-based study.

Lee YC, Lin CH, Wu RM, et al.
Neurology. 2013 Jul 30;81(5):410-416. Epub 2013 Jul 24

Background

The potent anti-inflammatory effects of statins are well-described [1-4]. Statins may also reduce intraneuronal alpha-synuclein aggregation in animal models of Parkinson’s Disease (PD) [5]. This has led to the hypothesis that statins may have a protective role for PD. At the same time, statins may also lower the level of plasma coenzyme Q10 (CoQ10), which may cancel out potential favourable effects [6].
Until now, studies examining the association between statin use and PD risk have yielded inconsistent results, possibly due to methodological weaknesses. This study benefitted from the fact that the Taiwan’s National Health Insurance Reimbursement Policy requested physicians to discontinue statin therapy once LDL levels were below 100 mg/dL. Thus, the effect of discontinuing statins on risk of PD was evaluated. A total of 43810 statin initiators were included in the analysis. 

Main results

• Incidence of PD was 1.68 and 3.52 per 1000000 person-days for lipophilic and hydrophilic statins, respectively.
• Continuing use of lipophilic statins was associated with a lower risk of PD, when compared to discontinuation of statins (adjHR: 0.42, 95%CI: 0.27-0.64). This protective effect seemed nonsignificantly more prominent in women than in men, without an obvious difference in age groups. A significantly reduced risk of PD was seen for simvastatin and atorvastatin, while lipophilic statins lovastatin and fluvastatin only showed a trend towards a reduced risk.
• There was no association between PD and use of hydrophilic statins.
• Mortality rates were analysed, to exclude the possibility that patients who continued to use statins would have higher LDL-c levels and therefore may have higher mortality rates, resulting in lower PD incidence. People continuing lipophilic statin use showed a lower risk of mortality than did people who discontinued  statins (HR: 0.31, 95%CI: 0.18-0.54), while continuing with a hydrophilic statin gave a tendency towards a reduced mortality risk as compared to discontinuation (HR: 0.48, 95%CI: 0.23-1.00).
• No dose or duration response relation between use of lipophilic statins and incidence of PD was seen in subgroups of men or women and those aged <65 or >65 years.

Conclusion

Continuing use of lipophilic statins is associated with a decreased risk of PD, as compared to discontinuation of statin use. Hydrophilic statins did not show a similar potential beneficial effect. Lipophilic statins more easily cross the blood-brain barrier. Good penetration into the brain could yield better antioxidant and anti-inflammatory effects.

Editorial comment [7]

This study benefitted from the comprehensive data available on statin and other medication use. However, no data was available on several potential modulatory effects of known protective lifestyle factors. Also, actual levels of cholesterol and lipids were not included in the analysis. While there is a biological basis for the association between statin use and PD, more research should further decipher the specific pathways or targets that are involved in statin-induced neuroprotection. In the meantime, for those who have to be on statins, it is a comforting thought that statins may have the advantage of having a lower risk of PD, and possibly other neurological disorders.  

References

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