Abstract
BACKGROUND: The apolipoprotein E (APOE) ε4 allele, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are well-established risk factors for dementia. Relationships between APOE and incidence of T2DM and CVD are not fully understood but may shed light on the mechanisms underlying dementia pathogenesis. METHODS: Postmenopausal women (N = 6 795) from the Women's Health Initiative hormone therapy clinical trial with APOE genotyping and no prior diagnosis of T2DM or CVD were included. We examined associations of APOE status (APOE2+ [ε2/ε2, ε2/ε3], APOE3 [ε3/ε3], and APOE4+ [ε4/ε4, ε3/ε4] carriers) with incidence of T2DM, coronary heart disease, stroke, and total CVD events using Cox regression. CVD outcomes were examined in baseline non-statin users and adjusted for statin initiation over follow-up to account for possible confounding by statins. RESULTS: Among all participants (mean age 66.7 ± 6.5 years, 100% non-Hispanic White), 451 (6.6%) were using statins at baseline. Over the follow-up (mean 14.9 and 16.0 years for T2DM and CVD, respectively), 1 564 participants developed T2DM and 1 578 developed CVD. T2DM incidence did not differ significantly by APOE status (ps ≥ .09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval] = 1.18 [1.02-1.38], p = .03) compared with APOE3 carriers, but risks for coronary heart disease (1.09 [0.87-1.36], p = .47) and stroke (1.14 [0.91-1.44], p = .27) were not significantly elevated when examined individually. CVD outcomes did not differ between APOE2+ and APOE3 carriers (ps ≥ 0.11). CONCLUSIONS: T2DM risk did not differ by APOE status among postmenopausal women, but APOE4+ carriers not using statins had an increased risk of total CVD events.