ApoE plasma levels and risk of cardiovascular mortality in old age.
ApoE plasma levels and risk of cardiovascular mortality in old age.
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DOI：
10.1371/journal.pmed.0030176
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发表时间：
2006-06
期刊：
影响因子：
15.8
通讯作者：
Westendorp, Rudi G. J.
中科院分区：
文献类型：
--
作者：
Mooijaart, Simon P.;Berbee, Jimmy F. P.;van Heemst, Diana;Havekes, Louis M.;de Craen, Anton J. M.;Slagboom, P. Eline;Rensen, Patrick C. N.;Westendorp, Rudi G. J.
载脂蛋白E基因（APOE）的等位基因分别编码三种亚型：apoE 2、E3和E4。apoE同种型以不同的血浆浓度循环，但相同同种型的血浆浓度在个体之间也不同。尽管同种型与心血管疾病有关，但血浆apoE水平与心血管疾病之间的关系尚不清楚。 我们评估了546名年龄在85岁以上的人的APOE基因型、血浆apoE水平、心血管危险因素和死亡率，这些人参加了莱顿85岁以上研究，并前瞻性随访了5年的特定死亡原因。apoE水平最高三分位数的参与者心血管死亡风险增加两倍（与最低三分位数相比，风险比为2.08; 95%置信区间[CI]为1.30至3.33）。在324名携带基因型为103/103的受试者中，心血管疾病的风险增加了3倍（最高与最低三分位数3.01; 95%CI 1.60至5.66），男性和女性的估计值相似。其他死因无明显增加。1993 - 1993年受试者的血浆apoE水平与总胆固醇（p < 0.001）、低密度脂蛋白胆固醇（p <0.001）和甘油三酯（p < 0.001）呈正相关，与高密度脂蛋白胆固醇水平呈负相关（p = 0.010）。调整血脂并没有改变风险比，而相互作用是不存在的。然而，与高水平apoE相关的风险在C-反应蛋白（CRP）水平最低的三分位数的参与者中最强，而在最高的三分位数的参与者中不存在（p相互作用< 0.001）。在CRP水平最低的三分位数的参与者中，apoE水平高的参与者的CRP水平比apoE水平低的参与者显著升高（p = 0.020）。在2002年和2004年的携带者中发现了与2003年参与者相似的心血管死亡风险。 在老年人中，高血浆apoE水平先于循环CRP的增加，并与心血管死亡率密切相关，与APOE基因型和血脂无关。 在一组85岁以上的人群中，apoE水平较高的人更有可能死于心血管疾病。所观察到的关联是独立的APOE基因型和血脂。
The ɛ2, ɛ3, and ɛ4 alleles of the apolipoprotein E gene (APOE) encode three isoforms, apoE2, E3, and E4, respectively. The apoE isoforms circulate in different plasma concentrations, but plasma concentrations of the same isoform also differ between individuals. Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown. We assessed APOE genotypes, plasma levels of apoE, cardiovascular risk factors, and mortality in a population-based sample of 546 individuals aged 85 y who participated in the Leiden 85-plus Study and were prospectively followed for specific causes of death for 5 y. Participants in the highest tertile of apoE levels suffered a twofold-increased risk of cardiovascular mortality (hazard ratio compared to lowest tertile, 2.08; 95% confidence interval [CI], 1.30 to 3.33). Among the 324 participants with the ɛ3ɛ3 genotype, the hazard from cardiovascular disease was threefold increased (highest versus lowest tertile 3.01; 95% CI 1.60 to 5.66), with similar estimates for men and women. Other causes of death were not increased significantly. Plasma levels of apoE in ɛ3ɛ3 participants were positively correlated with total cholesterol ( p < 0.001), low-density lipoprotein cholesterol ( p < 0.001) and triglycerides ( p < 0.001) and negatively with high-density lipoprotein cholesterol levels ( p = 0.010). Adjustment for plasma lipids did not change the hazard ratios, whereas interaction was absent. The risk associated with high levels of apoE, however, was strongest in participants from the lowest tertile of C-reactive protein (CRP) levels and absent in those from the highest tertile ( p interaction < 0.001). Among participants from the lowest tertile of CRP levels, those with a high apoE levels had a significantly steeper increase in CRP than those with low apoE levels ( p = 0.020). Similar cardiovascular mortality risks as in ɛ3ɛ3 participants were found in ɛ2 and ɛ4 carriers. In old age, high plasma apoE levels precede an increase of circulating CRP and strongly associates with cardiovascular mortality, independent of APOE genotype and plasma lipids. Among a cohort of people over 85 those with higher levels of apoE were more likely to die from cardiovascular disease. The observed association was independent of APOE genotype and plasma lipids.
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影响因子：
4.4
作者：
Lada, AT;Rudel, LL
通讯作者：
Rudel, LL
DOI：
10.1375/twin.5.2.87
发表时间：
2002-04-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Beekman, M;Heijmans, BT;Boomsma, DI
通讯作者：
Boomsma, DI
影响因子：
6.5
作者：
Cohn, JS;Rodriguez, C;Davignon, A
通讯作者：
Davignon, A
影响因子：
5.2
作者：
Haddy, N;De Bacquer, D;Visvikis, S
通讯作者：
Visvikis, S
影响因子：
15.9
作者：
Rensen, PCN;vanOosten, M;vanBerkel, TJC
通讯作者：
vanBerkel, TJC