Levy Andrew P, Friedenberg Paula, Lotan Rachel, Ouyang Pamela, Tripputi Mark, Higginson Lyall, Cobb Frederick R, Tardif Jean-Claude, Bittner Vera, Howard Barbara V
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Diabetes Care. 2004 Apr;27(4):925-30. doi: 10.2337/diacare.27.4.925.
Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography.
We tested this hypothesis in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status.
We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 +/- 0.040 mm, P = 0.049). This benefit was more marked in diabetic subjects (0.149 +/- 0.064 mm, P = 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 +/- 0.057 mm, P = 0.027). HRT had no effect on these outcomes.
The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.
抗氧化剂试验尚未证明其在减缓心血管疾病方面的疗效，但不能排除对特定患者亚组有益。抗氧化剂疗法可降低触珠蛋白1等位基因纯合子（Hp 1-1）中低密度脂蛋白的氧化能力，但对具有触珠蛋白2等位基因的个体（Hp 2-1或Hp 2-2）无效。因此，我们推测触珠蛋白类型可预测维生素疗法对冠状动脉粥样硬化的影响，该影响通过血管造影进行评估。
我们在女性血管造影维生素与雌激素（WAVE）试验中检验了这一假设，该试验是一项对绝经后女性使用维生素C和E加或不加激素替代疗法（HRT）的前瞻性血管造影研究。在299名接受了基线和随访血管造影的女性中确定了触珠蛋白类型。在按维生素使用情况、触珠蛋白类型和糖尿病状态分层的分析中，检查了最小管腔直径（MLD）的年化变化。
我们发现，与安慰剂相比，维生素疗法对Hp 1-1受试者的MLD变化有显著益处（0.079±0.040毫米，P = 0.049）。在糖尿病受试者中，这种益处更为明显（0.149±0.064毫米，P = 0.021）。另一方面，在Hp 2-2受试者中，维生素疗法使MLD有更快下降的趋势，在糖尿病受试者中更为明显（0.128±0.057毫米，P = 0.027）。HRT对这些结果没有影响。
在WAVE研究中，维生素疗法对女性冠状动脉狭窄进展的相对益处或危害取决于触珠蛋白类型。触珠蛋白类型的这种影响在糖尿病女性中似乎更强。
