Abstract
Background: Case reports have related the use of HMG-CoA reductase inhibitors (‘statins’) to Parkinson’s disease (PD). Paradoxically, however, statins may have potentially beneficial effects on neurodegenerative diseases due to their anti-inflammatory properties.
Objective: To explore the risk of the development of PD in association with untreated hyperlipidaemia and with hyperlipidaemia treated with lipid-lowering drugs in the UK primary care setting.
Methods: We conducted a case-control analysis using the UK-based General Practice Research Database (GPRD). Cases were incident PD cases ≥40 years of age between 1994 and 2005. One control was matched to each PD case based on age, sex, general practice and index date. Lipid-lowering drug use was assessed by exposure timing (current vs past use) and by exposure duration (1–9,10–29 or≥30 prescriptions) prior to the index date for both cases and controls. Odds ratios (OR) were calculated using conditional logistic regression, adjusted for body mass index, smoking and various cardiovascular, metabolic and psychiatric co-morbidities.
Results: We identified 3637 cases with an incident idiopathic PD diagnosis, and the same number of controls. Compared with patients without hyperlipidaemia, those with untreated hyperlipidaemia did not have an altered relative PD risk (adjusted OR 0.98, 95% CI 0.74, 1.30). The adjusted ORs for current use of ≥30 prescriptions for statins or fibrates compared with non-use of statins or fibrates were 1.06 (95% CI 0.75, 1.51) and 1.25 (95% CI 0.51, 3.06), respectively.
Conclusions: In this observational study, the long-term use of statins or fibrates was not associated with a substantially altered relative risk of developing PD.
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References
Lang AE, Lozano AM. Parkinson’s disease: first of two parts. N Engl J Med 1998; 339: 1044–53
Jenner P. Oxidative stress in Parkinson’s disease. Ann Neurol 2003; 53 Suppl. 3: S26–36; discussion S36-8
Hirsch EC, Hunot S, Hartmann A. Neuroinflammatory processes in Parkinson’s disease. Parkinsonism Relat Disord 2005; 11 Suppl. 1: S9–15
Schapira AH, Gu M, Taanman JW, et al. Mitochondria in the etiology and pathogenesis of Parkinson’s disease. Ann Neurol 1998; 44: S89–98
Selley ML. Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res 2005; 1037: 1–6
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005; 45: 89–118
Jick H, Zornberg GL, Jick SS, et al. Statins and the risk of dementia [erratum appears in Lancet 2001 Feb 17; 357 (9255): 562]. Lancet 2000; 356: 1627–31
Stepien K, Tomaszewski M, Czuczwar SJ. Neuroprotective properties of statins. Pharmacol Rep 2005; 57: 561–9
Rea TD, Breitner JC, Psaty BM, et al. Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol 2005; 62: 1047–51
Levesque LE, Delaney JA, Etminan M, et al. Pharmacologic interventions for the prevention of Alzheimer’s disease: an example of reverse protopathic bias [abstract no. 65]. 22nd International conference on pharmacoepidemiology and therapeutic risk management; 2006 Aug 24–27; Lisbon. Pharmacoepidemiol Drug Saf 2006; 15: S31
Muller T, Kuhn W, Pohlau D, et al. Parkinsonism unmasked by lovastatin. Ann Neurol 1995; 37: 685–6
Muller T. Statininduziertes Parkinson-Syndrom. Leserbrief zum Beitrag von J. Finsterer in “Der Nervenarzt” (2003) 74: 115–122. Nervenarzt 2003; 74: 726–7
Huang X, Chen H, Miller WC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson’s disease. Mov Disord 2007; 22: 377–81
de Lau LM, Koudstaal PJ, Hofman A, et al. Serum cholesterol levels and the risk of Parkinson’s disease. Am J Epidemiol 2006; 164: 998–1002
Jick H. A database worth saving. Lancet 1997; 350: 1045–6
Lawson DH, Sherman V, Hollowell J. The General Practice Research Database: scientific and ethical advisory group. QJM 1998; 91: 445–52
Wood L, Martinez C. The general practice research database: role in pharmacovigilance. Drug Saf 2004; 27: 871–81
Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the general practice research database. Pharmacotherapy 2003; 23: 686–9
Walley T, Mantgani A. The UK General Practice Research Database. Lancet 1997; 350: 1097–9
Hernan MA, Logroscino G, Rodriguez LA. A prospective study of alcoholism and the risk of Parkinson’s disease. J Neurol 2004; 251 Suppl. 7: vII14–7
Hernan MA, Logroscino G, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology 2006; 66: 1097–9
Lieberman A, Lyons K, Levine J, et al. Statins, cholesterol, coenzyme Q10, and Parkinson’s disease. Parkinsonism Relat Disord 2005; 11: 81–4
Rajanikant GK, Zemke D, Kassab M, et al. The therapeutic potential of statins in neurological disorders. Curr Med Chem 2007; 14: 103–12
Wang Q, Wang PH, McLachlan C, et al. Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats. Brain Res 2005; 1045: 229–33
Wang Q, Tang XN, Wang L, et al. Effects of high dose of simvastatin on levels of dopamine and its reuptake in prefrontal cortex and striatum among SD rats. Neurosci Lett 2006; 408: 189–93
Duits N, Bos FM. Depressive symptoms and cholesterol-lowering drugs. Lancet 1993; 341: 114
Tatley M, Savage R. Psychiatric adverse reactions with statins, fibrates and ezetimibe: implications for the use of lipid-lowering agents. Drug Saf 2007; 30: 195–201
Gregoor PJ. Atorvastatin may cause nightmares [letter]. BMJ 2006; 332: 950
Sinzinger H, Mayr F, Schmid P, et al. Sleep disturbance and appetite loss after lovastatin [letter]. Lancet 1994; 343: 973
Ernster L, Dallner G. Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1995; 1271: 195–204
Shults CW, Haas RH, Passov D, et al. Coenzyme Q10 levels correlate with the activities of complexes I and II/III in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol 1997; 42: 261–4
Schapira AH, Mann VM, Cooper JM, et al. Mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson’s Disease Research Group. Ann Neurol 1992; 32 Suppl.: S116–24
Kaikkonen J, Nyyssonen K, Tuomainen TP, et al. Determinants of plasma coenzyme Q10 in humans. FEBS Lett 1999; 443: 163–6
Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci USA 1990; 87: 8931–4
Ghirlanda G, Oradei A, Manto A, et al. Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors: a double-blind, placebo-controlled study. J Clin Pharmacol 1993; 33: 226–9
Laaksonen R, Ojala JP, Tikkanen MJ, et al. Serum ubiquinone concentrations after short-and long-term treatment with HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1994; 46: 313–7
Mortensen SA, Leth A, Agner E, et al. Dose-related decrease of serum coenzyme Q10 during treatment with HMG-CoA reductase inhibitors. Mol Aspects Med 1997; 18 Suppl.: S137–44
Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002; 59: 1541–50
Muller T, Buttner T, Gholipour AF, et al. Coenzyme Q10 supplementation provides mild symptomatic benefit in patients with Parkinson’s disease. Neurosci Lett 2003; 341: 201–4
Kreisler A, Gele P, Wiart JF, et al. Lipid-lowering drugs in the MPTP mouse model of Parkinson’s disease: fenofibrate has a neuroprotective effect, whereas bezafibrate and HMG-CoA reductase inhibitors do not. Brain Res 2007; 1135: 77–84
Frigerio R, Elbaz A, Sanft KR, et al. Education and occupations preceding Parkinson disease: a population-based case-control study. Neurology 2005; 65: 1575–83
OTC statins: a bad decision for public health. Lancet 2004; 363: 1659
Nefzger MD, Quadfasel FA, Karl VC. A retrospective study of smoking in Parkinson’s disease. Am J Epidemiol 1968; 88: 149–58
Quik M. Smoking, nicotine and Parkinson’s disease. Trends Neurosci 2004; 27: 561–8
Hancock DB, Martin ER, Stajich JM, et al. Smoking, caffeine, and nonsteroidal anti-inflammatory drugs in families with Parkinson disease. Arch Neurol 2007; 64: 576–80
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No sources of funding were used to conduct this study. None of the authors have any conflicts of interest directly relevant to the content of this study.
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Becker, C., Jick, S.S. & Meier, C.R. Use of Statins and the Risk of Parkinson’s Disease. Drug-Safety 31, 399–407 (2008). https://doi.org/10.2165/00002018-200831050-00004
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DOI: https://doi.org/10.2165/00002018-200831050-00004