Journal of Neurology

, Volume 255, Issue 7, pp 993–1000

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

  • D. Brenner
  • J. Labreuche
  • F. Pico
  • P. Scheltens
  • O. Poirier
  • F. Cambien
  • P. Amarenco
  • on behalf of the GENIC Investigators
ORIGINAL COMMUNICATION

DOI: 10.1007/s00415-008-0816-8

Cite this article as:
Brenner, D., Labreuche, J., Pico, F. et al. J Neurol (2008) 255: 993. doi:10.1007/s00415-008-0816-8

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.

Key words

small vessel disease renin-angiotensin-aldosterone system brain infarction genetics leukoaraiosis lacune 

Copyright information

© Springer 2008

Authors and Affiliations

  • D. Brenner
    • 1
    • 5
  • J. Labreuche
    • 1
  • F. Pico
    • 2
  • P. Scheltens
    • 3
  • O. Poirier
    • 4
  • F. Cambien
    • 4
  • P. Amarenco
    • 1
  • on behalf of the GENIC Investigators
  1. 1.INSERM-698 and Coordinating Centre for the GENIC study, Dept. of Neurology and Stroke CentreBichat University Hospital and Medical School, Denis Diderot UniversityParisFrance
  2. 2.Department of NeurologyVersailles Mignot HospitalVersaillesFrance
  3. 3.VU University Medical CenterAmsterdamThe Netherlands
  4. 4.INSERM 525Pitié-Salpêtrière Medical SchoolParisFrance
  5. 5.Dept. of NeurologyUniversity of Alabama at BirminghamBirminghamUSA

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