Apolipoprotein E ε2 Allele and Risk of Stroke in the Older Population

Abstract

Background and Purpose There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an ε4 allele and lower in those carrying an ε2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. Methods At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged ≥71 years and free of stroke were genotyped for apo E. Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. Results One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of ε3 and ε4 did not influence stroke risk. Among persons aged <80 years at the time of genotyping, ε2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with ε2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an ε2 had 2.6-fold higher risk of incident stroke, and those aged ≥80 years had even higher risks of stroke but without any difference according to presence/absence of ε2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages ≥80 years (94 events). Conclusions The conditioning influence of age on the protection conferred by the apoE ε2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.