Genetic and Environmental Risk Factors for Intracerebral Hemorrhage

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Abstract
Background and Purpose — Intracerebral hemorrhage (ICH) has a 30-day mortality rate of 40% to 50% and lacks a proven treatment. We report a preplanned, midpoint analysis of the first population-based, case-control study that examines both genetic and environmental risk factors of ICH. Methods — We prospectively identified cases of hemorrhagic stroke at all 16 hospitals in the Greater Cincinnati/Northern Kentucky region. All cases underwent medical record and neuroimaging review. Cases enrolled in the direct interview and genetic sampling arm of the study were matched to population-based control subjects by age, race, and sex. Multivariable logistic regression was performed to identify significant independent risk factors. Results — We enrolled 188 cases of ICH (67 lobar, 121 nonlobar) and 366 control subjects in the direct interview arm of the study. Significant independent risk factors for lobar ICH included the presence of an apolipoprotein E2 or E4 allele, frequent alcohol use, prior stroke, and first-degree relative with ICH. Significant independent risk factors for nonlobar ICH were hypertension, prior stroke, and first-degree relative with ICH. An increasing level of education was associated with a decreased risk of nonlobar ICH. The attributable risk of apolipoprotein E2 or E4 for lobar ICH was 29%, and the attributable risk of hypertension for nonlobar ICH was 54%. Conclusions — There is significant epidemiological evidence that the pathophysiology of ICH varies by location. We estimate that a third of all cases of lobar ICH are attributable to possession of an apolipoprotein E4 or E2 allele and that half of all cases of nonlobar ICH are attributable to hypertension.