O'Donnell H C, Rosand J, Knudsen K A, Furie K L, Segal A Z, Chiu R I, Ikeda D, Greenberg S M
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
N Engl J Med. 2000 Jan 27;342(4):240-5. doi: 10.1056/NEJM200001273420403.
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.
复发性脑叶脑出血是脑淀粉样血管病的标志。促使患者脑叶出血早期复发的因素尚不清楚。一个可能的因素是载脂蛋白E基因，因为载脂蛋白E的ε2和ε4等位基因似乎都与淀粉样血管病的严重程度相关。
我们对连续的老年脑叶脑出血存活患者进行了一项前瞻性纵向研究。通过每6个月进行一次访谈以及查阅病历和计算机断层扫描来随访患者是否发生复发性出血性卒中。
在平均23.9±14.8个月的随访期内，71名登记患者中有19名发生了复发性出血，2年累积复发率为21%。载脂蛋白E基因型与复发风险显著相关。ε2或ε4等位基因携带者的2年复发率为28%，而常见的载脂蛋白E ε3/ε3基因型患者的复发率仅为10%（风险比为3.8；95%置信区间为1.2至11.6；P = 0.01）。8例患者发生早期复发，其中4例具有罕见的ε2/ε4基因型。研究入组前有出血性卒中病史的患者复发风险也增加（2年复发率为61%；风险比为6.4；95%置信区间为2.2至18.5；P<0.001）。
载脂蛋白E基因型可识别脑叶脑出血早期复发风险最高的患者。这一发现既可为脑叶出血患者提供预后信息，也为靶向和评估潜在预防策略提供了一种方法。
