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The renin-angiotensin-aldosterone system in cerebral small vessel disease

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Abstract

Introduction

Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), état criblé (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 Génétique de l’Infarctus Cérébral (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, 0.31– 1.05) and severe LA (adjusted OR, 0.54; 95 % CI, 0.30–0.95), 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, 1.02–1.53).

Conclusions

This exploratory study found no strong evidence for RAAS involvement in severe SVD in this population. The whole spectrum of SVD, including EC, MLI, and LA, can be considered as phenotypes for genetic studies.

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Authors and Affiliations

  1. INSERM-698 and Coordinating Centre for the GENIC study, Dept. of Neurology and Stroke Centre, Bichat University Hospital and Medical School, Denis Diderot University, 46, rue Henri Huchard, 75018, Paris, France

    D. Brenner MD, J. Labreuche Bst &  P. Amarenco MD

  2. Department of Neurology, Versailles Mignot Hospital, Versailles, France

    F. Pico MD

  3. VU University Medical Center, Amsterdam, The Netherlands

    P. Scheltens MD

  4. INSERM 525, Pitié-Salpêtrière Medical School, Paris, France

    O. Poirier PhD & F. Cambien MD

  5. Dept. of Neurology, University of Alabama at Birmingham, Birmingham, USA

    D. Brenner MD

Authors
  1. D. Brenner MD
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  2. J. Labreuche Bst
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  3. F. Pico MD
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  4. P. Scheltens MD
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  5. O. Poirier PhD
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  6. F. Cambien MD
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  7. P. Amarenco MD
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on behalf of the GENIC Investigators

Corresponding author

Correspondence to P. Amarenco MD.

Additional information

The institutions and investigators in theGENIC (Étude du profil GENétique del’Infarctus Cérébral) study are listed on ourwebsite: http://www.ccr.jussieu.fr/GENIC/Welcome.html.

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Brenner, D., Labreuche, J., Pico, F. et al. The renin-angiotensin-aldosterone system in cerebral small vessel disease. J Neurol 255, 993–1000 (2008). https://doi.org/10.1007/s00415-008-0816-8

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  • DOI: https://doi.org/10.1007/s00415-008-0816-8

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