Apolipoprotein E ε4 Allele Interacts with Sex and Cognitive Status to Influence All-Cause and Cause-Specific Mortality in U.S. Older Adults
Apolipoprotein E ε4 Allele Interacts with Sex and Cognitive Status to Influence All-Cause and Cause-Specific Mortality in U.S. Older Adults
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DOI：
10.1111/jgs.12156
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发表时间：
2013-04-01
影响因子：
6.3
通讯作者：
Zonderman, Alan B.
中科院分区：
文献类型：
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作者：
Beydoun, May A.;Beydoun, Hind A.;Zonderman, Alan B.
目的 确认载脂蛋白 E (ApoE) epsilon 4 携带者状态、性别和时间依赖性认知状态与死亡风险的关联，并在社区居住的美国成年人队列中研究这些关联的联合效应。设计前瞻性队列研究。设置巴尔的摩老龄化纵向研究（BLSA）。参与者 首次就诊时年龄在 17 至 98 岁之间的 3,047 名 BLSA 参与者（60.1% 为男性）中，有 1,704 名具有完整的 ApoE 基因型数据，其中 1,461 名年龄在 50 岁及以上且有过一次或多次就诊的参与者符合资格。测量所有心血管和非心血管原因导致的死亡时间。结果 ApoE epsilon 4 携带者的生存概率较低，尤其是年龄较大的携带者。全因死亡率的 Cox 比例风险模型得出 ApoE epsilon 4 携带者与非携带者的风险比 (HR) 为 1.31（95% 置信区间 (CI)=1.021.68）。心血管死亡率也存在这种关联。时间依赖性全因痴呆（HR=1.73，95% CI=1.332.26）和轻度认知障碍（HR=1.95，95% CI=1.422.67）增加全因死亡风险，也检测到与非心血管死亡的关联。当个体没有认知障碍时，发现全因死亡率与 epsilon 4 等位基因存在剂量反应关系（对于 1 epsilon 4，HR=1.40，95% CI=0.942.07；对于 2 epsilon 4，HR=2.61，95% CI=1.126.07）。阿尔茨海默病 (AD) 发病后，仅携带一种 epsilon 4 等位基因会导致全因死亡风险比非携带者高约 77%。 ApoE epsilon 4 携带者状态增加了男性全因死亡风险，并与时间依赖性 AD 相互作用，增加了这一结果的风险（由于相互作用导致的相对超额风险=2.15，95% CI=1.223.07）。结论 ApoE epsilon 4 携带者状态会增加全因死亡率和心血管死亡风险，并与性别和时间依赖性 AD 状态相互作用，影响全因死亡率。
Objectives To confirm associations of apolipoprotein E (ApoE) epsilon 4 carrier status, sex, and time-dependent cognitive status with mortality risk and to investigate these joint effects of these associations in a cohort of community-dwelling U.S. adults. Design Prospective cohort study. Setting The Baltimore Longitudinal Study of Aging (BLSA). Participants Of 3,047 BLSA participants aged 17 to 98 at first visit (60.1% male), 1,704 with complete ApoE genotype data were included, of whom 1,461 aged 50 and older with one or more visits were eligible. Measurements Time to death from all, cardiovascular, and noncardiovascular causes. Results Probability of survival was lower for ApoE epsilon 4 carriers, particularly those who were older. A Cox proportional hazards model for all-cause mortality yielded a hazard ratio (HR) for ApoE epsilon 4 carrier versus noncarriers of 1.31 (95% confidence interval (CI)=1.021.68). This association was also found for cardiovascular mortality. Time-dependent all-cause dementia (HR=1.73, 95% CI= 1.332.26) and mild cognitive impairment (HR=1.95, 95% CI=1.422.67) increased all-cause mortality risk, associations that were also detected for noncardiovascular mortality. When individuals were free of cognitive impairment, a dose-response relationship with epsilon 4 alleles was found for all-cause mortality (HR=1.40, 95% CI=0.942.07 for 1 epsilon 4; HR=2.61, 95% CI=1.126.07 for 2 epsilon 4). After onset of Alzheimer's disease (AD), carrying only one epsilon 4 allele resulted in an approximately 77% greater all-cause mortality risk than in noncarriers. ApoE epsilon 4 carrier status increased all-cause mortality risk in men and interacted with time-dependent AD to increase the risk of this outcome (relative excess risk due to interaction=2.15, 95% CI=1.223.07). Conclusion ApoE epsilon 4 carrier status was found to increase all-cause and cardiovascular mortality risks and interacted with sex and time-dependent AD status to affect all-cause mortality.