Background: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. Methods: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. Results: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4–16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01–0.82) independently predicted the development of new brain infarcts. Conclusions: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct.

Prabhakaran S, Wright CB, Yoshita M, Delapaz R, Brown T, DeCarli C, Sacco RL: Prevalence and determinants of subclinical brain infarction: The Northern Manhattan Study. Neurology 2008;70:425–430.
Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM: Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke 2003;34:392–396.
Bryan RN, Wells SW, Miller TJ, Elster AD, Jungreis CA, Poirier VC, Lind BK, Manolio TA: Infarct-like lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly – data from the Cardiovascular Health Study. Radiology 1997;202:47–54.
Vermeer SE, Longstreth WT Jr, Koudstaal PJ: Silent brain infarcts: a systematic review. Lancet Neurol 2007;6:611–619.
Leary MC, Saver JL: Annual incidence of first silent stroke in the United States: a preliminary estimate. Cerebrovasc Dis 2003;16:280–285.
Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR: Lacunar infarcts defined by magnetic resonance imaging of 3,660 elderly people: the Cardiovascular Health Study. Arch Neurol 1998;55:1217–1225.
Bernick C, Kuller L, Dulberg C, Longstreth WT Jr, Manolio T, Beauchamp N, Price T: Silent MRI infarcts and the risk of future stroke: the Cardiovascular Health Study. Neurology 2001;57:1222–1229.
Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM: Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 2003;34:1126–1129.
Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM: Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 2003;348:1215–1222.
Van Dijk EJ, Prins ND, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM: Progression of cerebral small vessel disease in relation to risk factors and cognitive consequences: Rotterdam Scan Study. Stroke 2008;39:2712–2719.
Hachinski V: World stroke day 2008: ‘little strokes, big trouble’. Stroke 2008;39:2407–2420.
Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383–1389.
Taylor AJ, Kent SM, Flaherty PJ, Coyle LC, Markwood TT, Vernalis MN: Arbiter: Arterial biology for the investigation of the treatment effects of reducing cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness. Circulation 2002;106:2055–2060.
Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006;355:549–559.
Bernick C, Katz R, Smith NL, Rapp S, Bhadelia R, Carlson M, Kuller L: Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology 2005;65:1388–1394.
Mok VC, Lam WW, Chen XY, Wong A, Ng PW, Tsoi TH, Yeung V, Liu R, Soo Y, Leung TW, Wong KS: Statins for asymptomatic middle cerebral artery stenosis: the regression of cerebral artery stenosis study. Cerebrovasc Dis 2009;28:18–25.
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22.
Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT: Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990;323:1289–1298.
Amarenco P, Labreuche J, Lavallee P, Touboul PJ: Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke 2004;35:2902–2909.
Mok VC, Lam WW, Fan YH, Wong A, Ng PW, Tsoi TH, Yeung V, Wong KS: Effects of statins on the progression of cerebral white matter lesion: post-hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study. J Neurol 2009;256:750–757.
Ii M, Losordo DW: Statins and the endothelium. Vasc Pharmacol 2007;46:1–9.
Essig M, Nguyen G, Prie D, Escoubet B, Sraer JD, Friedlander G: 3-Hydroxy-3-methylglutaryl coenzyme a reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and rho proteins. Circ Res 1998;83:683–690.
Sugiyama T, Lee JD, Shimizu H, Abe S, Ueda T: Influence of treated blood pressure on progression of silent cerebral infarction. J Hypertens 1999;17:679–684.
Hasegawa Y, Yamaguchi T, Omae T, Woodward M, Chalmers J: Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan. Hypertens Res 2004;27:147–156.
Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Ebihara I, Koide H: Silent cerebral infarction in patients with type 2 diabetic nephropathy. Effects of antiplatelet drug dilazep dihydrochloride. Diabetes Metab Res Rev 2005;21:39–43.
Shinoda-Tagawa T, Yamasaki Y, Yoshida S, Kajimoto Y, Tsujino T, Hakui N, Matsumoto M, Hori M: A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with type II diabetes. Diabetologia 2002;45:188–194.
Das RR, Seshadri S, Beiser AS, Kelly-Hayes M, Au R, Himali JJ, Kase CS, Benjamin EJ, Polak JF, O’Donnell CJ, Yoshita M, D’Agostino RB Sr, DeCarli C, Wolf PA: Prevalence and correlates of silent cerebral infarcts in the Framingham Offspring Study. Stroke 2008;39:2929–2935.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.