Woodward Mark, Croft Kevin D, Mori Trevor A, Headlam Henrietta, Wang Xiao Suo, Suarna Cacang, Raftery Mark J, MacMahon Stephen W, Stocker Roland
Department of Medicine, Mount Sinai Medical Center, New York, NY 10029-6574, USA.
Clin Sci (Lond). 2009 Jan;116(1):53-60. doi: 10.1042/CS20070404.
The role of oxidative damage in the aetiology of coronary disease remains controversial, as clinical trials investigating the effect of antioxidants have not generally been positive. In the present study, 227 coronary cases, identified from a cohort study, were matched, by age and gender, with 420 controls in a nested case-control design. Stored plasma samples were analysed for F2-isoprostanes by stable isotope dilution MS, and specifically oxidized forms of apoA-I (apolipoprotein A-I) by HPLC of HDL (high-density lipoprotein). Median values of F2-isoprostanes were higher in plasma samples that contained oxidized apoA-I compared with samples with undetectable oxidized apoA-I (1542 compared with 1165 pmol/l). F2-Isoprostanes were significantly correlated with variants of non-oxidized apoA-II (r=-0.15) and were associated with HDL-cholesterol (P<0.0001). F2-Isoprostanes in cases (median, 1146 pmol/l) were not different from controls (1250 pmol/l); the odds ratio (95% confidence interval) for a 1 S.D. increase in F2-isoprostanes was 1.08 (0.91-1.29). Similarly, there was no independent association between the presence of oxidized apoA-I, detected in approx. 20% of the samples, and coronary risk. In conclusion, we found no evidence of associations between markers of lipid (F2-isoprostanes) and protein (oxidized apoA-I) oxidation and the risk of fatal or non-fatal coronary heart disease in a general population. This may be due to a true lack of association or insufficient power.
氧化损伤在冠心病病因学中的作用仍存在争议，因为调查抗氧化剂作用的临床试验总体上并不乐观。在本研究中，从一项队列研究中确定的227例冠心病患者，在巢式病例对照设计中，按年龄和性别与420名对照进行匹配。通过稳定同位素稀释质谱法分析储存的血浆样本中的F2-异前列腺素，并通过高密度脂蛋白（HDL）的高效液相色谱法分析载脂蛋白A-I（apoA-I）的特定氧化形式。与未检测到氧化apoA-I的样本相比，含有氧化apoA-I的血浆样本中F2-异前列腺素的中位数更高（分别为1542和1165 pmol/l）。F2-异前列腺素与未氧化的apoA-II变体显著相关（r = -0.15），并与HDL胆固醇相关（P<0.0001）。病例组中F2-异前列腺素的中位数（1146 pmol/l）与对照组（1250 pmol/l）无差异；F2-异前列腺素每增加1个标准差的优势比（95%置信区间）为1.08（0.91 - 1.29）。同样，在约20%的样本中检测到的氧化apoA-I的存在与冠心病风险之间没有独立关联。总之，在普通人群中，我们没有发现脂质（F2-异前列腺素）和蛋白质（氧化apoA-I）氧化标志物与致命或非致命冠心病风险之间存在关联的证据。这可能是由于真正缺乏关联或检验效能不足。
