Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.
Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.
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DOI：
10.2217/pgs.10.17
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发表时间：
2010-05
期刊：
影响因子：
2.1
通讯作者：
Levy AP
中科院分区：
文献类型：
--
作者：
Blum S;Vardi M;Brown JB;Russell A;Milman U;Shapira C;Levy NS;Miller-Lotan R;Asleh R;Levy AP
同时具有糖尿病（DM）和结合珠蛋白（Hp）2-2基因型的个体患心血管疾病的风险增加。由于Hp 2-2蛋白的抗氧化功能受损，我们试图验证药物基因组学假设，即抗氧化剂维生素E补充剂可为Hp 2-2 DM个体提供心血管保护。我们确定了两项试验（HOPE和ICARE）中DM参与者的Hp基因型，并通过Hp基因型评估了维生素E对他们共同的预先指定结局（卒中、心肌梗死和心血管死亡）的影响。采用固定效应模型分析数据。这些结果被输入到模拟模型中，即循证医学集成器，以估计其在Kaiser Permanente（CA，USA）真实世界人群中的长期影响。两项试验的荟萃分析表明，维生素E治疗的Hp 2-2型糖尿病患者的复合终点总体显著降低（比值比：0.58; 95% CI：0.40-0.86; p = 0.006）。在复合终点，Hp基因型和维生素E之间存在统计学显著的相互作用。在这些试验中，对69名糖尿病患者进行了Hp分型，并用维生素E治疗Hp 2-2患者，预防了1例心肌梗死、中风或心血管死亡。在Kaiser人群中，对Hp 2-2 DM个体终身给予维生素E将使其预期寿命增加3年。药物基因组学策略筛选糖尿病个体的Hp基因型和治疗Hp 2-2与维生素E似乎是高度临床有效的。
Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40–0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years. A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective.
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影响因子：
7.7
作者：
Asleh R;Blum S;Kalet-Litman S;Alshiek J;Miller-Lotan R;Asaf R;Rock W;Aviram M;Milman U;Shapira C;Abassi Z;Levy AP
通讯作者：
Levy AP
DOI：
10.1161/01.atv.0000251020.24399.a2
发表时间：
2007-01-01
影响因子：
8.7
作者：
Levy, Andrew P.;Levy, Joanne E.;Moreno, Pedro R.
通讯作者：
Moreno, Pedro R.
影响因子：
168.9
作者：
Mihaylova, B;Briggs, A;Collins, R
通讯作者：
Collins, R
影响因子：
6.6
作者：
Asleh, Rabea;Levy, Andrew P.
通讯作者：
Levy, Andrew P.
影响因子：
7.7
作者：
Costacou, Tina;Ferrell, Robert E.;Orchard, Trevor J.
通讯作者：
Orchard, Trevor J.