Apolipoprotein E genotype and the risk of recurrent lobar intracerebral hemorrhage

Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
New England Journal of Medicine (Impact Factor: 54.42). 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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Available from: Heather C O'Donnell, Aug 02, 2015
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    • "Hemorrhages in locations characteristic of hypertensive vasculopathy, such as basal ganglia, thalamus, or brainstem also recur, but less frequently [8]. Other factors associated with P-ICH recurrence include age [4], absence of anti-platelet medication after stroke [9], previous hemorrhage before the presenting P-ICH [7], possession of the apolipoprotein E␧2 or ␧4 alleles [7] [10], and a greater number of microbleeds by T2- weighted gradient-echo magnetic resonance imaging (MRI) [11]. Furthermore, use of post-ICH anticoagulant was reported to triple the risk of a hemorrhagic event [4]. "
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    • "Conversely, the yearly risk of hypertensive ICH recurrence is approximately 2% [Bailey et al. 2001] whereas that due to amyloid angiopathy ranges from 5% to 15%, depending on genetic predisposition [O&apos;Donnell et al. 2000]. While risk of ICH recurrence does not appear to be increased by aspirin [Viswanathan et al. 2006], the risk may be tripled by warfarin [Vermeer et al. 2002]. "
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    • "Unfortunately, despite a number of preclinical studies reporting positive results, no drugs have been translated into human treatments (Badjatia & Rosand, 2005). An important concern is that ICH is mainly a disease of the elderly (Collins et al., 2003), in whom there are increases in the major predisposing factors: chronic hypertension and amyloid angiopathy (O'Donnell et al., 2000; Ariesen et al., 2003). Despite this, experimental models have almost exclusively used young animals. "
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