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

J Neurol. 2008 Jul;255(7):993-1000. doi: 10.1007/s00415-008-0816-8. Epub 2008 May 2.


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 renin-angiotensin-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cerebrovascular Disorders / blood
  • Cerebrovascular Disorders / diagnosis
  • Cerebrovascular Disorders / genetics*
  • Cerebrovascular Disorders / physiopathology
  • Confidence Intervals
  • Cytochrome P-450 CYP11B2 / genetics
  • Female
  • Genotype
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Odds Ratio
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic*
  • Receptor, Angiotensin, Type 2 / genetics
  • Renin-Angiotensin System / genetics*
  • Renin-Angiotensin System / physiology
  • Retrospective Studies


  • Receptor, Angiotensin, Type 2
  • Cytochrome P-450 CYP11B2
  • Peptidyl-Dipeptidase A