Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.
Apolipoprotein E genotypes and response of plasma lipids and progression-regression of coronary atherosclerosis to lipid-lowering drug therapy.
复制标题
DOI：
10.1016/s0735-1097(00)00918-9
复制
发表时间：
2000-11
影响因子：
24
通讯作者：
C. Ballantyne;J. Herd;E. Stein;L. Ferlic;J. Dunn;A. Gotto;A. Marian
中科院分区：
文献类型：
--
作者：
C. Ballantyne;J. Herd;E. Stein;L. Ferlic;J. Dunn;A. Gotto;A. Marian
目的：在脂蛋白与冠状动脉粥样硬化研究(LCAS)中，我们试图研究载脂蛋白E(Apo E)基因与基础血脂水平和冠状动脉疾病(CAD)严重程度的关系，以及对氟伐他汀治疗的反应。然而，载脂蛋白E基因对轻度至中度胆固醇升高患者的血脂反应和他汀类药物治疗后冠心病进展或退化的影响尚不清楚。320名受试者在氟伐他汀或安慰剂治疗12周后测定血脂。结果与3/4或4/4基因携带者相比，3/3基因携带者的总胆固醇(20.4%vs.15.4%，p=0.01)和低密度脂蛋白(LDL)胆固醇(28.8%vs.22.7%，p=0.03)的降幅更大。相反，携带2/3基因的受试者(n=10)的高密度脂蛋白胆固醇水平(19.1%)高于携带3/3基因的受试者(4.3%，p=0.002)和携带3/4或4/4基因的受试者(7.0%，p=0.02)。携带3/4或4/4等位基因的受试者接受血管成形术的频率较高，但基础冠心病严重程度和基础血脂的其他指标在不同基因型间没有显著差异，冠心病进展或临床事件也没有显著差异。结论尽管携带ϵ4等位基因的受试者服用氟伐他汀降低低密度脂蛋白胆固醇的程度较小，但他们在冠心病进展方面具有相似的益处。
OBJECTIVESWe sought to examine the association of apolipoprotein (apo) E genotypes with baseline plasma lipid levels and severity of coronary artery disease (CAD), as well as the response to treatment with fluvastatin in the Lipoprotein and Coronary Atherosclerosis Study (LCAS).BACKGROUNDApo E genotypes have been associated with plasma lipid levels and CAD. However, the influence of apo E genotypes on the response of plasma lipids and CAD progression or regression to statin treatment in patients with mildly to moderately elevated cholesterol remains unknown.METHODSApo E genotypes were determined by polymerase chain reaction and restriction mapping. Plasma lipids were measured at baseline and 12 weeks after therapy with fluvastatin or placebo in 320 subjects. In 287 subjects, quantitative coronary angiography was performed at baseline and after 2.5 years of treatment.RESULTSSubjects with the 3/3 genotype had greater reductions in total cholesterol (20.4% vs. 15.4%, p = 0.01) and low density lipoprotein (LDL) cholesterol (28.8% vs. 22.7%, p = 0.03) than did the subjects with the 3/4 or 4/4 genotype. In contrast, subjects with the 2/3 genotype (n = 10) had a greater increase in high density lipoprotein cholesterol (19.1%) than did the subjects with the 3/3 genotype (4.3%, p = 0.002) and those with the 3/4 or 4/4 genotype (7.0%, p = 0.02). Subjects with the 3/4 or 4/4 genotype had an increased frequency of previous angioplasty, but other measures of baseline CAD severity and baseline lipids did not differ significantly among the genotypes, nor did CAD progression or clinical events.CONCLUSIONSAlthough subjects with the ϵ4 allele had less reduction in LDL cholesterol with fluvastatin, they had similar benefit in terms of CAD progression.