To our knowledge, this is the first demonstration of a sex effect of APOE variation in a cardiovascular disease phenotype, which is of value when considering the relatively nascent concept of an aging, sex, and APOE triad.60 Sex-specific differences in APOE-e genotypes associations with Alzheimer disease have been noted (summarized by Fisher et al61), with female carriers of APOE-e3/e4 demonstrating increased risk of Alzheimer disease and faster decline than their male counterparts. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.