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 (CHD), 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≥0.09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval]=1.18 [1.02-1.38], p=0.03) compared to APOE3 carriers, but risks for CHD (1.09 [0.87-1.36], p=0.47) and stroke (1.14 [0.91-1.44], p=0.27) 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.

中文翻译：

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绝经后妇女 APOE、2 型糖尿病和心血管疾病之间的关系


背景 载脂蛋白 E (APOE) ε4 等位基因、2 型糖尿病 (T2DM) 和心血管疾病 (CVD) 是痴呆症的明确危险因素。 APOE 与 T2DM 和 CVD 发病率之间的关系尚不完全清楚，但可能有助于揭示痴呆发病机制。方法 纳入来自妇女健康倡议激素治疗临床试验的绝经后妇女 (N=6,795)，进行 APOE 基因分型，且之前未诊断出 T2DM 或 CVD。我们检查了 APOE 状态（APOE2+ [ε2/ε2、ε2/ε3]、APOE3 [ε3/ε3] 和 APOE4+ [ε4/ε4、ε3/ε4] 携带者）与 T​​2DM、冠心病 (CHD)、使用 Cox 回归分析中风和总 CVD 事件。在基线非他汀类药物使用者中检查了 CVD 结果，并在随访期间根据他汀类药物的起始情况进行了调整，以解释他汀类药物可能造成的混淆。结果 在所有参与者（平均年龄 66.7±6.5 岁，100% 非西班牙裔白人）中，451 人 (6.6%) 在基线时使用他汀类药物。在随访期间（T2DM 和 CVD 的平均时间分别为 14.9 年和 16.0 年），1,564 名参与者发展为 T2DM，1,578 名参与者发展为 CVD。 APOE 状态不同，T2DM 发病率没有显着差异 (ps≥0.09)。在非他汀类药物使用者中，与 APOE3 携带者相比，APOE4+ 的总 CVD 发生率较高（风险比 [95% 置信区间]=1.18 [1.02-1.38]，p=0.03），但 CHD 风险较高（1.09 [0.87-1.36]） ，p=0.47）和中风（1.14 [0.91-1.44]，p=0.27）单独检查时没有显着升高。 APOE2+ 和 APOE3 携带者的 CVD 结果没有差异 (ps≥0.11)。结论 在绝经后妇女中，T2DM 风险并不因 APOE 状态而异，但不使用他汀类药物的 APOE4+ 携带者发生总 CVD 事件的风险增加。