Currently Viewing:
The American Journal of Managed Care August 2013
Cost of Care for Malignant and Benign Renal Masses
Aviva G. Asnis-Alibozek, PA-C; Michael J. Fine, MD; Paul Russo, MD; Trent McLaughlin, BSc(Pharm), PhD; Eileen M. Farrelly, MPH; Norman LaFrance, MD; and William Lowrance, MD, MPH
Currently Reading
Long-Term Statin Use and the Risk of Parkinson's Disease
Bitya Friedman, MD; Amnon Lahad, MD, MPH; Yizchak Dresner, MD, MS; and Shlomo Vinker, MD
Does Medication Adherence Lead to Lower Healthcare Expenses for Patients With Diabetes?
Shou-Hsia Cheng, PhD; Chi-Chen Chen, PhD; and Chin-Hsiao Tseng, MD, PhD
False Activation of the Cardiac Catheterization Laboratory for Primary PCI
Geoffrey D. Barnes, MD; Alexander Katz, MD; Jeffrey S. Desmond, MD; Steven L. Kronick, MD, MS; Jamie Beach, RN; Stanley J. Chetcuti, MD; Eric R. Bates, MD; and Hitinder S. Gurm, MD
Option Pricing: A Flexible Tool to Disseminate Shared Savings Contracts
Mark W. Friedberg, MD, MPP; Anthony M. Buendia, BA; Katharine E. Lauderdale, BA; and Peter S. Hussey, PhD
Sources of Information Used in Selection of Surgeons
Caroline S. Carlin, PhD; John Kralewski, PhD; and Megan Savage, BS
A Natural Experiment in Mass Media Modulated Pharmacokinetics After a Change in Tablet Formulation
Natan R. Kahan, PhD, RPh, MHA; Daniel A. Vardy, MD, MSc; Dan-Andrei Waitman, MD, MPH; and Gherta Brill, MD

Long-Term Statin Use and the Risk of Parkinson's Disease

Bitya Friedman, MD; Amnon Lahad, MD, MPH; Yizchak Dresner, MD, MS; and Shlomo Vinker, MD
This historical cohort study demonstrates that long-term statin use is associated with a significant decrease in the incidence of Parkinson's disease.
A few studies over the past years have examined the possible association between statin use and PD. However, their findings vary widely, as discussed in the introduction. Our historical prospective cohort study was designed to overcome some of the weaknesses of previous studies. One  advantage was that it enabled us to show a temporal association between the exposure (cholesterol level and statin use) and the outcome (a new diagnosis of PD). Another advantage of choosing a cohort design was reduction of selection bias. A population-based study based on data from unselected medical files from primary care clinics reflects the epidemiology of the disease more accurately than casecontrol studies.

One of the main advantages of this study is its use of objective data, without reliance on patient-reported information or even physician-reported diagnosis. All information— laboratory tests, medical diagnoses, and drug purchase—was obtained from a computerized database. In this way we minimized potential information bias.

The statistical power of this study is high due to the large size of the cohort and the number of patients with incident PD, which is the largest number reported in any prospective study to date. There have been studies with larger cohorts and longer periods of observation (eg, Simon and colleaues14); however, the number of incident cases of PD was smaller, probably due to the younger ages of subjects included and the larger proportion of women.

In our study we were able to show that long-term statin use was associated strongly with a significant decrease in PD incidence (OR, 0.73; P = .001). No association was found between baseline LDL-C levels and risk of PD.

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.

CONCLUSIONS

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: bityaf@gmail.com.
1. Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations. 2005 through 2030. Neurology. 2007;68(5):384-386.

2. Xu Q, Park Y, Huang X, et al. Diabetes and risk of Parkinson’s disease. Diabetes Care. 2011;34(4):910-915.

3. Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J. Type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care. 2007;30(4): 842-847.

4. Hu G, Jousilahti P, Nissinen A, Antikainen R, Kivipelto M, Tuomilehto J. Body mass index and the risk of Parkinson disease. Neurology. 2006;67(11):1955-1999.

5. Logroscino G, Sesso HD, Paffenbarger RS Jr, Lee IM. Body mass index and risk of Parkinson’s disease: a prospective cohort study. Am J Epidemiol. 2007;166(10):1186-1190.

6. Qiu C, Hu G, Kivipelto M, et al. Association of blood pressure and hypertension with the risk of parkinson disease: the National FINRISK/Study. Hypertension. 2011;57(6):1094-1100.

7. Ritz B, Ascherio A, Checkoway H, et al. Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol. 2007;64(7):990-997.

8. Thacker EL, O’Reilly EJ, Weisskopf MG, et al. Temporal relationship between cigarette smoking and risk of Parkinson disease. Neurology. 2007;68(10):764-768.

9. Huang X, Chen H, Miller WC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson’s disease. Mov Disord. 2007;22(3):377-381.

10. de Lau LM, Koudstaal PJ, Hofman A, Breteler MM. Serum cholesterol levels and the risk of Parkinson’s disease. Am J Epidemiol. 2006; 164(10):998-1002.

11. Huang X, Abbott RD, Petrovitch H, Mailman RB, Ross W. Low LDL cholesterol and increased risk of Parkinson’s disease: prospective results from Honolulu-Asia Aging Study. Mov Disord. 2008;23(7):1013-1038.

12. Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Statin use and the risk of Parkinson disease. Neurology. 2008;70(16, pt 2):1418-1422.

13. Ritz B, Manthripragada AD, Qian L, et al. Statin use and Parkinson’s disease in Denmark. Mov Disord. 2010;25(9):1210-1216.

14. Simon KC, Chen H, Schwarzschild M, Ascherio A. Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease. Neurology. 2007;69(17):1688-1695.

15. Gao X, Simon KC, Schwarzschild MA, Ascherio A. Prospective study of statin use and risk of Parkinson disease. Arch Neurol. 2012;69(3): 380-384.

16. Samii A, Carleton BC, Etminan M. Statin use and the risk of Parkinson disease: a nested case control study. J Clin Neurosci. 2008;15(11): 1272-1273.

17. Armitage J. The safety of statins in clinical practice. Lancet. 2007; 370(9601):1781.

18. Ward S, Lloyd Jones M, Pandor A, et al. A systematic review and economic evaluation of statins for the prevention of coronary events. Health Technol Assess. 2007;11(14):1-160.

19. Roy A, Pahan K. Prospects of statins in Parkinson disease. Neuroscientist. 2011;17(3):244-255.

20. Ghosh A, Roy A, Matras J, Brahmachari S, Gendelman HE, Pahan K. Simvastatin inhibits the activation of p21ras and prevents the loss of dopaminergic neurons in a mouse model of Parkinson’s disease. J Neurosci. 2009;29(43):13543-13556.

21. Bar-On P, Crews L, Koob AO, et al. Statins reduce neuronal alphasynuclein aggregation in in vitro models of Parkinson’s disease. J Neurochem. 2008;105(5):1656-1667.

22. Lieberman A, Lyons K, Levine J, Myerburg R. Statins, cholesterol, co-enzyme Q10, and Parkinson’s disease. Parkinsonism Relat Disord. 2005;11(2):81-84.

23. Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G. Coenzyme Q10 in neuromuscular and neurodegenerative disorders. Curr Drug Targets. 2010;11(1):111-121.

24. Huang X, Chen PC, Poole C. APOE-[epsilon]2 allele associated with higher prevalence of sporadic Parkinson disease. Neurology. 2004; 62(12):2198-2202.

25. Wilson PW, Myers RH, Larson MG, Ordovas JM, Wolf PA, Schaefer EJ. Apolipoprotein E alleles, dyslipidemia, and coronary heart disease: the Framingham Offspring Study. JAMA 1994;272(21):1666-1671.

26. Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology. 2008;70(21): 1972-1979.

27. Rennert G, Peterburg Y. Prevalence of selected chronic diseases in Israel. Isr Med Assoc J. 2001;3(6):404-408.

28. Tabenkin, H. Clinical guidelines: Israeli task-force recommendations for health promotion and preventive health services. http://www.ima.org.il/Ima/FormStorage/Type1/clinical_09_preventive.pdf. Published 2008. Accessed January 2009.

29. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.

30. Rao SR, Schoenfeld DA. Survival methods. Circulation. 2007;115(1): 109-113.

31. Orr JD. Statins in the spectrum of neurologic disease. Curr Atheroscler Rep. 2008;10(1):11-18.

32. Thanvi B, Lo N, Robinson T. Vascular parkinsonism—an important cause of parkinsonism in older people. Age Ageing. 2005;34(2):114-119.

33. Rektor I, Rektorová I, Kubová D. Vascular parkinsonism—an update. J Neurol Sci. 2006;248(1-2):185-191.

34. Elbaz A, Moisan F. Update in the epidemiology of Parkinson’s disease. Curr Opin Neurol. 2008;21(4):454-460.

35. Lees AJ, Hardy J, Revesz T. Parkinson’s disease [published correction appears in Lancet. 2009;374(9691):684]. Lancet. 2009;373(9680): 2055-2066.

36. Shulman LM, Bhat V. Gender disparities in Parkinson’s disease. Expert Rev Neurother. 2006;6(3):407-416.
PDF
 
Copyright AJMC 2006-2019 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
x
Welcome the the new and improved AJMC.com, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up