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J Neurol (2008) 255:9931000DOI 10.1007/s00415-008-0816-8 ORIGINAL COMMUNICATION
The renin-angiotensin-aldosterone system in cerebral small vessel disease
David BrennerJulien Labreuche Fernando PicoPhilip Scheltens Odette Poirier Franois Cambien Pierre Amarencoon behalf of the GENIC
Investigators
Received: 5 July 2007Received in revised form: 1 November 2007 Accepted: 13 November 2007Published online: 2 May 2008
D. Brenner, MD J. Labreuche, Bst
Prof. P. Amarenco, MD ([L53175]) INSERM-698 and Coordinating Centre for the GENIC studyDept. of Neurology and Stroke Centre Bichat University Hospitaland Medical SchoolDenis Diderot University46, rue Henri Huchard75018 Paris, FranceTel.: +33-1/49952591Fax: +33-1/49952596E-Mail: [email protected]
F. Pico, MDDepartment of Neurology Versailles Mignot Hospital Versailles, France
P. Scheltens, MDVU University Medical Center Amsterdam, The Netherlands
O. Poirier, PhD F. Cambien, MD INSERM 525Piti-Salptrire Medical School Paris, France
D. Brenner, MDDept. of NeurologyUniversity of Alabama at Birmingham, USA
The institutions and investigators in the GENIC (tude du profil GENtique de lInfarctus Crbral) study are listed on our website: http://www.ccr.jussieu.fr/GENIC/ Welcome.html.
Abstract Introduction Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), tat cribl (EC), and multiple lacunar infarctions (MLI). Although the pathophysiology of SVD is poorly understood, there is evidence of a genetic contribution. We sought to analyze the influence of the reninangiotensin-aldosterone system (RAAS) on SVD in symptomatic patients from the Gntique de lInfarctus Crbral (GENIC) study, including RAAS polymorphisms and circulating angiotensin converting enzyme (ACE). Methods Caucasian patients (n = 510) with acute brain infarction (BI) were recruited and MRIs were evaluated for SVD, including LA, EC, and MLI. We considered ACE levels and several polymorphisms, including ACE, angiotensinogen, aldosterone
synthase CYP11B2, and angiotensin II receptor type I. Results Among the polymorphisms, there were marginal negative associations between aldosterone synthase CYP11B2 -344C against severe EC (adjusted OR, 0.57; 95 % CI, 0.311.05) and severe LA (adjusted OR, 0.54; 95 % CI, 0.300.95), both considering -344C dominant. In addition, the frequency of -344C decreased with the number of SVD abnormalities (p = 0.016). Mean plasma ACE was elevated in patients with MLI, but not with LA or EC. The risk of MLI increased gradually with increasing plasma ACE (adjusted OR, 1.25; 95 % CI, 1.021.53). Conclusions This exploratory study found no strong evidence for RAAS involvement in severe SVD in this population. The whole spectrum of SVD,...