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

Introduction Cerebral small vessel disease (SVD) appears on magnetic resonance imaging (MRI) as leukoaraiosis (LA), etat crible (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 Genetique de l'Infarctus Cerebral (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 MLL 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.