Article

Apolipoprotein E Genotype and the Risk of Recurrent Lobar Intracerebral Hemorrhage

Harvard University, Cambridge, Massachusetts, United States
New England Journal of Medicine (Impact Factor: 55.87). 02/2000; 342(4):240-5. DOI: 10.1056/NEJM200001273420403
Source: PubMed

ABSTRACT

Recurrent lobar intracerebral hemorrhage is the hallmark of cerebral amyloid angiopathy. The factors that predispose patients to early recurrence of lobar hemorrhage are unknown. One candidate is the apolipoprotein E gene, since both the epsilon2 and the epsilon4 alleles of apolipoprotein E appear to be associated with the severity of amyloid angiopathy.
We performed a prospective, longitudinal study of consecutive elderly patients who survived a lobar intracerebral hemorrhage. The patients were followed for recurrent hemorrhagic stroke by interviews at six-month intervals and reviews of medical records and computed tomographic scans.
Nineteen of 71 enrolled patients had recurrent hemorrhages during a mean follow-up period of 23.9+/-14.8 months, yielding a 2-year cumulative rate of recurrence of 21 percent. The apolipoprotein E genotype was significantly associated with the risk of recurrence. Carriers of the epsilon2 or epsilon4 allele had a two-year rate of recurrence of 28 percent, as compared with only 10 percent for patients with the common apolipoprotein E epsilon3/epsilon3 genotype (risk ratio, 3.8; 95 percent confidence interval, 1.2 to 11.6; P=0.01). Early recurrence occurred in eight patients, four of whom had the uncommon epsilon2/epsilon4 genotype. Also at increased risk for recurrence were patients with a history of hemorrhagic stroke before entry into the study (two-year recurrence, 61 percent; risk ratio, 6.4; 95 percent confidence interval, 2.2 to 18.5; P<0.001).
The apolipoprotein E genotype can identify patients with lobar intracerebral hemorrhage who are at highest risk for early recurrence. This finding makes possible both the provision of prognostic information to patients with lobar hemorrhage and a method of targeting and assessing potential strategies for prevention.

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    • "Previous studies have established that different underlying pathologies are associated with the specific location of hemorrhage in the brain [3]. ICH located in deep brain regions (deep ICH) is a result of rupture of small arterioles most commonly in the putamen or thalamus [4] [5] [6], while ICH in lobar locations (lobar ICH), results from rupture of small and medium-sized arterial perforators in the cortex and subcortical white matter [7]. While deep perforating vasculopathy (including arteriolosclerosis, lipohyalinosis and fibrinoid necrosis, mainly driven by traditional cardiovascular risk factors) appears to underlie deep ICH [3], cerebral amyloid angiopathy (CAA), resulting from progressive cerebrovascular β-amyloid (Aβ) deposition within small cortical and leptomeningeal small vessel walls, accounts for the majority of lobar ICH in the elderly [8] [9] [10] [11]. "
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    • "Patients commonly present with an acute stroke syndrome with focal neurological deficits that may be associated with headache, vomiting, seizures and/or an altered level of consciousness. In the longer term, survivors of lobar ICHs are at a high risk of recurrence, especially with the presence of the ε2 or ε4 alleles of the apolipoprotein E gene (28 % cumulative recurrence rate at 2 years relative to 10 % in patients without either allele) [17]. "
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    • "Ten to 20% of strokes are caused by ICH in Western countries.6) Over 45 years of age, ICH is common,5)16)21) but rare before then. Therefore, the goal of our study was to perform a descriptive analysis of ICH etiology and prognostic factors in patients aged ≤ 40 years. "
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