APOLIPOPROTEIN-E POLYMORPHISM AND SILENT MICROANGIOPATHY-RELATED CEREBRAL-DAMAGE - RESULTS OF THE AUSTRIAN STROKE PREVENTION STUDY

Background and Purpose Microangiopathy-related cerebral damage (MARCD) includes white matter abnormalities and lacunar infarctions and repre sents a common MRI observation in subjects above 50 years of age. The risk factors of such brain abnormalities are not fully determined. The goal of this study was to determine whether the genetic heterogeneity of apolipoprotein E (apoE) contributes to the occurrence of MARCD. Me thods Brain MRI (1.5 T) was performed in 280 individuals (ages 50 to 7 5 years) without neuropsychiatric disease randomly selected from the o fficial register of residents of the city of Graz, Austria. All study participants underwent apoE genotyping, carotid Doppler sonography, el ectrocardiography, echocardiography, and a complete blood chemistry pa nel. MARCD was defined as evidence of early confluent and confluent wh ite matter hyperintensities or lacunes. Carotid atherosclerosis was gr aded on a five-point scale ranging from not present (0) to complete oc clusion (5). Results MARCD occurred in 61 individuals (21%). The distr ibution of apoE genotypes differed significantly between subjects with and without MARCD (P=.036). Subjects with such findings more commonly had the epsilon 2/epsilon 3 genotype (24.6% versus 10%) at similar fr equencies of genotypes containing the epsilon 4 allele. The epsilon 2/ epsilon 3 genotype was associated with lower levels of total cholester ol (P=.0009), LDL cholesterol (P=.00001), and apolipoprotein B (P=.000 01). Also, there was a nonsignificant trend toward less cardiac diseas e. Other major vascular risk factors and carotid abnormalities were si milar among the various genotypes. Multiple logistic regression analys is created a model of significant MARCD predictors, including age (odd s ratio [OR], 1.1 per year), hypertension (OR, 3.4), and the apoE epsi lon 2/epsilon 3 genotype (OR, 3.0). Conclusions These data suggest an association between the apoE epsilon 2/epsilon 3 genotype and MARCD de spite favorable effects on the lipid profile and cardiac disease.