Background: Axonal damage and inflammatory demyelination both occur in multiple sclerosis (MS). Some studies suggest that statins, through pleiotropic effects, reduce inflammatory episodes and protect neurons. However, other studies suggest statins have disparate impacts on these pathologic processes.
Objective: The objective of this study was to assess disability progression in MS patients receiving statin therapy.
Methods: We performed a retrospective medical record review of an established population-based MS prevalence cohort in Olmsted County, Minnesota, comparing disability progression between patients receiving statins and controls.
Results: Duration of statin use ranged from 1.9 to 20.3 years with a mean and standard deviation of 6.8 ± 4 years. Years between assessments ranged from 0.6 to 8.2 (75% of patients having intervals >6.4 years). The median (interquartile range) absolute change of disability among the statin group was 0 (0 to +1), compared with +0.5 (0, +1) in the no-statin group. Distributions were not significantly different (p = 0.39). The mean (standard deviation) absolute change of disability scores among the statin group was +0.69 (+1.49), not significantly different from +0.61 (+1.31) in the no-statin group. Likewise, annualized disability scores did not differ significantly (p = 0.23). Eighteen (40%) patients worsened by 1.0 or more on Expanded Disability Status Scale (EDSS) in the statin group and 36 (40%) in the no-statin group (p = 0.85, chi-squared test).
Conclusions: In this cohort, disability progression did not differ between those receiving statin therapy and controls. These findings support the hypothesis that statins, in doses currently prescribed for hyperlipidemia, do not affect the long-term course of MS.
CompstonA. The basis for treatment in multiple sclerosis. Acta Neurol Scand Suppl2006; 183: 41–47.
2.
SadeghiMMTiglioASadighK. Inhibition of interferon-gamma-mediated microvascular endothelial cell major histocompatibility complex class II gene activation by HMG-CoA reductase inhibitors. Transplantation2001; 71: 1262–1268.
3.
YoussefSStuveOPatarroyoJC. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature2002; 420: 78–84.
4.
Weitz-SchmidtGWelzenbachKBrinkmannV. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med2001; 7: 687–692.
5.
Johnson-AnunaLNEckertGPKellerJH. Chronic administration of statins alters multiple gene expression patterns in mouse cerebral cortex. J Pharmacol Exp Ther2005; 312: 786–793.
6.
Johnson-AnunaLNEckertGPFrankeCIgbavboaUMullerWEWoodWG.Simvastatin protects neurons from cytotoxicity by up-regulating Bcl-2 mRNA and protein. J Neurochem2007; 101: 77–86.
7.
MironVERajasekharanSJarjourAAZamvilSSKennedyTEAntelJP.Simvastatin regulates oligodendroglial process dynamics and survival. Glia2007; 55: 130–143.
8.
FooteAKBlakemoreWF. Inflammation stimulates remyelination in areas of chronic demyelination. Brain2005; 128: 528–539.
9.
BjorkhemIMeaneyS. Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol2004; 24: 806–815.
10.
JurevicsHMorellP. Cholesterol for synthesis of myelin is made locally, not imported into brain. J Neurochem1995; 64: 895–901.
11.
SaherGBruggerBLappe-SiefkeC. High cholesterol level is essential for myelin membrane growth. Nat Neurosci2005; 8: 468–475.
12.
MaierODe JongeJNomdenAHoekstraDBaronW. Lovastatin induces the formation of abnormal myelin-like membrane sheets in primary oligodendrocytes. Glia2009; 57: 402–413.
13.
StanislausRPahanKSinghAKSinghI. Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci Lett1999; 269: 71–74.
14.
MironVEZehntnerSPKuhlmannT. Statin therapy inhibits remyelination in the central nervous system. Am J Pathol2009; 174: 1880–1890.
15.
SenaAPedrosaRGraca MoraisM. Therapeutic potential of lovastatin in multiple sclerosis. J Neurol2003; 250: 754–755.
ToghaMKarvighSANabaviM. Simvastatin treatment in patients with relapsing-remitting multiple sclerosis receiving interferon beta 1a: a double-blind randomized controlled trial. Mult Scler2010; 16: 848–854.
19.
BirnbaumGCreeBAltafullahIZinserMRederAT. Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis. Neurology2008; 71: 1390–1395.
20.
PittockSJMayrWTMcClellandRL. Disability profile of MS did not change over 10 years in a population-based prevalence cohort. Neurology2004; 62: 601–606.
21.
PoserCMPatyDWScheinbergL. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol1983; 13: 227–231.
22.
StuartEA. Matching methods for causal inference: A review and a look forward. Stat Sci2010; 25: 1–21.
23.
MarrieRARudickRHorwitzR. Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology2010; 74: 1041–1047.
