Mänttäri M, Manninen V, Huttunen J K, Palosuo T, Ehnholm C, Heinonen O P, Frick M H
First Department of Medicine, University of Helsinki, Finland.
Eur Heart J. 1994 Dec;15(12):1599-603. doi: 10.1093/oxfordjournals.eurheartj.a060440.
Iron and copper catalyze lipid peroxidation in vitro, and recent epidemiological data suggest that these metal ions might also be involved in human coronary heart disease. We tested the hypothesis by investigating whether the storage proteins ferritin and ceruloplasmin were coronary risk factors. A nested case-control study was set up in middle-aged dyslipidaemic participants of the Helsinki Heart Study: a placebo-controlled coronary primary prevention trial with gemfibrozil. Of the 140 subjects with cardiac end-points (non-fatal myocardial infarction or cardiac death) 136 were matched with controls for geographical area and drug treatment (gemfibrozil-placebo). Frozen baseline serum samples were used in the analyses of ferritin and ceruloplasmin. Using logistic regression analyses no increment in coronary risk was detected with increasing ferritin levels (P = 0.8 for trend). Ceruloplasmin was higher 349 +/- 86 vs 317 +/- 77 mg.l-1 (P < 0.001) in cases than in controls and the risk in the highest tertile was two-fold (odds ratio 2.1; 95% CI 1.1-4.2) compared to the lowest (P < 0.005 for trend). The risk of high ceruloplasmin was influenced by lipoprotein cholesterol concentrations, with an odds ratio of 2.4 (95% CI 1.3-4.4) in subjects with high low density lipoprotein cholesterol and of 11.3 (95% CI 2.5-52.2) in subjects with low high density lipoprotein cholesterol. It was concluded that ferritin was not associated with coronary heart disease in dyslipidaemic, middle-aged men, while there was a continuous and graded increment in coronary risk with elevating ceruloplasmin level.
铁和铜在体外可催化脂质过氧化,近期的流行病学数据表明,这些金属离子可能也与人类冠心病有关。我们通过研究储存蛋白铁蛋白和铜蓝蛋白是否为冠心病危险因素来验证这一假设。在赫尔辛基心脏研究的中年血脂异常参与者中开展了一项巢式病例对照研究,该研究是一项使用吉非贝齐的安慰剂对照冠心病一级预防试验。在140例有心脏终点事件(非致命性心肌梗死或心源性死亡)的受试者中,136例按地理区域和药物治疗(吉非贝齐-安慰剂)与对照组进行匹配。采用冷冻的基线血清样本分析铁蛋白和铜蓝蛋白。通过逻辑回归分析,未发现随着铁蛋白水平升高冠心病风险增加(趋势P = 0.8)。病例组的铜蓝蛋白水平高于对照组,分别为349±86与317±77 mg·L-1(P < 0.001),最高三分位数组的风险是最低三分位数组的两倍(比值比2.1;95%可信区间1.1 - 4.2)(趋势P < 0.005)。高铜蓝蛋白的风险受脂蛋白胆固醇浓度影响,在低密度脂蛋白胆固醇水平高的受试者中比值比为2.4(95%可信区间1.3 - 4.4),在高密度脂蛋白胆固醇水平低的受试者中比值比为11.3(95%可信区间2.5 - 52.2)。研究得出结论,在血脂异常的中年男性中,铁蛋白与冠心病无关,而随着铜蓝蛋白水平升高,冠心病风险持续且分级增加。