RELATION OF SERUM LIPOPROTEIN(A) CONCENTRATION AND APOLIPOPROTEIN(A) PHENOTYPE TO CORONARY HEART-DISEASE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA
RELATION OF SERUM LIPOPROTEIN(A) CONCENTRATION AND APOLIPOPROTEIN(A) PHENOTYPE TO CORONARY HEART-DISEASE IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA
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DOI：
10.1056/nejm199005243222104
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发表时间：
1990-05-24
影响因子：
158.5
通讯作者：
UTERMANN, G
中科院分区：
文献类型：
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作者：
SEED, M;HOPPICHLER, F;UTERMANN, G
家族性高胆固醇血症显著增加冠心病（CHD）的风险，但个体之间对冠心病的易感性存在相当大的差异。为了研究脂蛋白(a)作为冠心病危险因素的可能作用，我们研究了115例杂合子家族性高胆固醇血症患者血清脂蛋白(a)水平、载脂蛋白(a)遗传类型（影响脂蛋白(a)水平）与冠心病之间的关系。54例冠心病患者的中位脂蛋白(a)水平为57 mg /分升，明显高于61例非冠心病患者的相应值18 mg /分升。根据判别函数分析，脂蛋白(a)水平是两组之间的最佳鉴别指标（与所有其他脂质和脂蛋白水平、年龄、性别和吸烟状况相比）。对109例患者进行载脂蛋白(a)表型分型。载脂蛋白(a)表型和等位基因的频率在冠心病患者和非冠心病患者之间存在显著差异。与高脂蛋白(a)水平相关的等位基因LpS2在冠心病患者中更为常见（0.33比0.12）。相比之下，与低脂蛋白(a)水平相关的LpS4等位基因在无冠心病患者中更为常见（0.27 vs 0.15）。我们的结论是，脂蛋白(a)水平升高是家族性高胆固醇血症患者发生冠心病的一个重要危险因素，且风险的增加与年龄、性别、吸烟状况、血清总胆固醇、甘油三酯或高密度脂蛋白胆固醇水平无关。在冠心病患者中观察到的较高水平的脂蛋白(a)是遗传影响的结果。
Familial hypercholesterolemia carries a marked increase in the risk of coronary heart disease (CHD), but there is considerable variation between individuals in susceptibility to CHD. To investigate the possible role of lipoprotein(a) as a risk factor for CHD, we studied the association between serum lipoprotein(a) levels, genetic types of apolipoprotein(a) (which influence lipoprotein(a) levels), and CHD in 115 patients with heterozygous familial hypercholesterolemia. The median lipoprotein(a) level in the 54 patients with CHD was 57 mg per deciliter, which is significantly higher than the corresponding value of 18 mg per deciliter in the 61 patients without CHD. According to discriminant-function analysis, the lipoprotein(a) level was the best discriminator between the two groups (as compared with all other lipid and lipoprotein levels, age, sex, and smoking status). Phenotyping for apolipoprotein(a) was performed in 109 patients. The frequencies of the apolipoprotein(a) phenotypes and alleles differed significantly between the patients with and those without CHD. The allele LpS2, which is associated with high lipoprotein(a) levels, was found more frequently among the patients with CHD (0.33 vs. 0.12). In contrast, the LpS4 allele, which is associated with low lipoprotein(a) levels, was more frequent among those without CHD (0.27 vs. 0.15). We conclude that an elevated level of lipoprotein(a) is a strong risk factor for CHD in patients with familial hypercholesterolemia, and the increase in risk is independent of age, sex, smoking status, and serum levels of total cholesterol, triglyceride, or high-density lipoprotein cholesterol. The higher level of lipoprotein(a) observed in the patients with CHD is the result of genetic influence.