GangHu, MD, PhD, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finlandhu.gang@ktl.fi
Riitta Antikainen, PhD (Oulu, Finland); Pekka Jousilahti, PhD; Miia. Kivipelto, PhD (Stockholm, Sweden); Jaakko Tuomilehto, PhD (Sein?joki, Finland)
Submitted June 04, 2008
We appreciate the comments from Mascitelli et al. on our findings. [1] They question whether lowering cholesterol with statins might increase the risk of incident PD and provide an interesting theory.
Autoimmune response against auto-antigens is beneficial while preventing the disease (PD). Tregs can suppress this beneficial response while promoting the disease. Tregs have been found to increase with age and statin use. Thus, statins may prevent the beneficial autoimmune response and increase the risk of PD.
Mascitelli et al. also consider that the association between high cholesterol and PD risk could be partially explained by the use of statins. Several epidemiologic studies have recently shown that high serum cholesterol is associated with an increased risk of dementia and AD. [6,7] One recent case-control study has also indicated that statin use may be associated with a lower PD occurrence, but the relatively small sample size (124 PD cases and 112 controls) may limit the statistical power. [8]
Information on the use of cholesterol-lowering agents in our study was obtained from the 1992 and 1997 surveys but not the earlier surveys of 1972-1987. To eliminate the possible effect of statin treatment on the incidence of PD, we performed a sensitivity analysis including the surveys from 1972 to 1992 (n=42,991) which were followed to the end of 1995. The use of statin therapy was minimal among Finns before 1996. After exclusion of participants who used cholesterol-lowering agents at baseline (n=103), sex- and multivariate-adjusted hazard ratios of PD at different levels of total cholesterol (<_5 _5-5.9="_5-5.9" _6-6.9="_6-6.9" and="and" mmol="mmol" l="l" were="were" _1.00="_1.00" _1.54="_1.54" _95="_95" ci="ci" _0.94-2.52="_0.94-2.52" _1.46="_1.46" _0.90-2.37="_0.90-2.37" _1.98="_1.98" _1.23-3.20="_1.23-3.20" p="p" for="for" trend="0.009)."/>No prospective studies or large clinical trials have assessed the association between use of statins and the risk of PD. Further studies are needed to test this hypothesis since we do not have data on the use of cholesterol-lowering agents during follow-up.
References
6. Notkola IL, Sulkava R, Pekkanen J, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology 1998;17:14-20.
7. Kivipelto M, Helkala EL, Laakso MP, et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002;137:149-155.
8. Huang X, Chen H, Miller WC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov Disord 2007;22:377-381.
We appreciate the comments from Mascitelli et al. on our findings. [1] They question whether lowering cholesterol with statins might increase the risk of incident PD and provide an interesting theory.
Autoimmune response against auto-antigens is beneficial while preventing the disease (PD). Tregs can suppress this beneficial response while promoting the disease. Tregs have been found to increase with age and statin use. Thus, statins may prevent the beneficial autoimmune response and increase the risk of PD.
Mascitelli et al. also consider that the association between high cholesterol and PD risk could be partially explained by the use of statins. Several epidemiologic studies have recently shown that high serum cholesterol is associated with an increased risk of dementia and AD. [6,7] One recent case-control study has also indicated that statin use may be associated with a lower PD occurrence, but the relatively small sample size (124 PD cases and 112 controls) may limit the statistical power. [8]
Information on the use of cholesterol-lowering agents in our study was obtained from the 1992 and 1997 surveys but not the earlier surveys of 1972-1987. To eliminate the possible effect of statin treatment on the incidence of PD, we performed a sensitivity analysis including the surveys from 1972 to 1992 (n=42,991) which were followed to the end of 1995. The use of statin therapy was minimal among Finns before 1996. After exclusion of participants who used cholesterol-lowering agents at baseline (n=103), sex- and multivariate-adjusted hazard ratios of PD at different levels of total cholesterol (<_5 _5-5.9="_5-5.9" _6-6.9="_6-6.9" and="and" mmol="mmol" l="l" were="were" _1.00="_1.00" _1.54="_1.54" _95="_95" ci="ci" _0.94-2.52="_0.94-2.52" _1.46="_1.46" _0.90-2.37="_0.90-2.37" _1.98="_1.98" _1.23-3.20="_1.23-3.20" p="p" for="for" trend="0.009)."/>No prospective studies or large clinical trials have assessed the association between use of statins and the risk of PD. Further studies are needed to test this hypothesis since we do not have data on the use of cholesterol-lowering agents during follow-up.
References
6. Notkola IL, Sulkava R, Pekkanen J, et al. Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease. Neuroepidemiology 1998;17:14-20.
7. Kivipelto M, Helkala EL, Laakso MP, et al. Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease. Ann Intern Med 2002;137:149-155.
8. Huang X, Chen H, Miller WC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov Disord 2007;22:377-381.
Disclosure: The authors report no disclosures.