APOE genotype, ethnicity, and the risk of cerebral hemorrhage

OBJECTIVE: The apolipoprotein E (APOE) polymorphism is an established risk factor for intracerebral hemorrhage (ICH) that is related to cerebral amyloid angiopathy in the white population. Among Asian populations, although ICH represents up to one third of all strokes and has high rates of mortality and morbidity, the role of the APOE polymorphism has not been well studied. METHODS: The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial of a blood pressure lowering regimen in subjects with prior cerebrovascular disease. APOE status was determined for 5,671 patients, including 2,148 Asians (38%). RESULTS: During the 3.9 years of follow-up, ICH occurred in 99 patients. Overall, carrying an ε2 or ε4 allele of the APOE polymorphism was associated with an adjusted hazard ratio (HRa) of 1.85 (95% CI = 1.24 to 2.76). In Asian patients the risk of ICH for ε2 or ε4 carriers was 2.11 (95% CI = 1.28 to 3.47) and 1.48 (95% CI = 0.76 to 2.87) in Europeans. Carriers of the ε2 or ε4 allele had an increased risk of both incident and recurrent ICH, and both cortical and deep ICH, and most risk estimates were higher in Asians than in Europeans. For both ethnic groups and for subtypes of ICH active treatment more than halved the risk of ICH and the treatment effects were not different in carriers of the ε2 or ε4 allele and in those with the ε3ε3 genotype. CONCLUSIONS: There is a strong association between APOE genotype and the risk of intracerebral hemorrhage (ICH). In Asian patients the role of APOE polymorphisms in ICH is much broader than was previously supposed.