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 epsilon 4 allele and lower in those carrying an epsilon 2 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 > or = 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 epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged > or = 80 years had even higher risk of stroke but without any difference according to presence/absence of epsilon 2 (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 > or = 80 years (94 events). CONCLUSIONS: The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.