Long-Term Statin Use and the Risk of Parkinson’s Disease | Page 3
Published Online: August 12, 2013
Bitya Friedman, MD; Amnon Lahad, MD, MPH; Yizchak Dresner, MD, MS; and Shlomo Vinker, MD
These findings suggest that in addition to their effectiveness in reducing cardiovascular risk, statins may also have a beneficial role in reducing the risk of PD. Clinically, this strengthens the benefit-risk ratio of statins. Another important implication is the understanding of the etiology and pathophysiology of PD. The association between statins and PD strengthens theories suggesting an influence of vascular factors on neurodegenerative diseases.31
This approach is supported by another finding in the present study: the strong association found between past history of CVA and the risk of PD (relative risk 1.97; 95% CI, 1.68-2.29; P <.001). However, the association found between CVA and PD incidence may be due to the method of defining PD in our study. Despite manual review of medical files and the exclusion of cases of secondary parkinsonism from the study, it is possible that some of the subjects who were diagnosed with PD actually suffered from parkinsonism due to vascular causes. Vascular parkinsonism is a parkinsonian syndrome caused by cerebrovascular disease. Its clinical and pathologic characteristics are different from those of PD, but it is probably underdiagnosed. The prevalence of vascular parkinsonism is estimated to be 4% to 12% of all parkinsonian syndromes.32
The main causes of secondary parkinsonism (as opposed to idiopathic PD) are medications and cerebrovascular disease. We defined our cohort as excluding patients treated with antipsychotic drugs, which may cause extrapyramidal symptoms. We did not exclude patients with a history of CVA. However, only a small minority of patients suffering from parkinsonian symptoms actually have vascular parkinsonism. It is more likely to find a common incidence of PD and cerebrovascular diseases, both of which present in the same age groups. It is not possible to suggest a pathophysiologic association between the 2 diseases solely on the basis of their chronological appearance.33
In this study, we were not able to show a dose-related association between statin use and PD incidence. Extent of exposure to statins was measured as years of statin use. The majority of subjects were exposed to statins for a period of up to 2.5 years due to the limited time of follow-up; the 2 other groups (2.5-4 years, >4 years) contained significantly fewer subjects. For example, the group that received statins for more than 4 years consisted of 2830 subjects, with an estimated incidence of fewer than 30 PD cases during the study period. The small size of these subgroups did not enable a statistically significant subgroup analysis, which is probably why we could not show a dose-related association between the exposure and the disease. Future studies would likely be able to test more patients who had protracted use of statins.
Several other variables were found to be associated with the incidence of PD. Male sex was related to an increased incidence of PD (OR, 1.58)—a finding consistent with previous studies.34-36
Socioeconomic status was found to be inversely related to PD risk, with low socioeconomic status associated with a higher rate of PD. However, the importance of this finding is limited in the context of the present study, due to a very narrow definition of socioeconomic status (ie, exemption from social security fees).
Interestingly, in a number of previous studies smoking was found to be a protective factor for PD.7,8,34 In our study we did not find a significant association between these variables.
In this study we were able to show a clear association between exposure to statins and PD incidence. The statins were found to have a protective effect, and their use was associated with an important and significant decrease in the incidence of PD.
Our results provide evidence confirming the lower incidence of PD among statin users. These findings warrant further research regarding the possible neuroprotective role of statins in PD and other neurodegenerative diseases. These results may also raise the possibility of statin use for the prevention of PD, especially as statins are known to be safe, inexpensive, and widely available.
Author Affiliations: From Psychiatric Division (BF), Herzog Hospital, Jerusalem, Israel; Hebrew University-Hadassah Medical School (BF), Departmentof Family Medicine (AL), Jerusalem, Israel; Clalit Health Services, Jerusalem (AL), Tel Aviv (YD, SV), Israel; Department of Family Medicine (YD, SV), Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Funding Source: None.
Author Disclosures: Dr Lahad reports the receipt of consulting fees from Pfizer for advisory boards and lecture fees. The other authors (BF, YD, SV) report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.
Authorship Information: Concept and design (BF, YD, SV); acquisition of data (BF, SV); analysis and interpretation of data (BF, AL); drafting of the manuscript (BF, AL, YD); critical revision of the manuscript for important intellectual content (AL, YD, SV); statistical analysis (BF, AL, SV); and supervision (AL, YD).
Address correspondence to: Bitya Friedman, MD, Herzog Hospital, Giv’at Sha’ul, POB 3900, Jerusalem 91035, Israel. E-mail: firstname.lastname@example.org.
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