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4S研究亚组中伴有脂质三联征及单纯高LDL胆固醇的冠心病患者的胆固醇合成与吸收

Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup.

作者信息

Miettinen Tatu A, Gylling Helena

机构信息

Department of Medicine, Division of Internal Medicine, University of Helsinki, Biomedicum Helsinki, C 4 22, Haartmaninkatu 8, PL 700 00029 HUS Helsinki, Finland.

出版信息

Atherosclerosis. 2003 Jun;168(2):343-9. doi: 10.1016/s0021-9150(03)00106-0.

Abstract

We assumed that assaying serum cholesterol precursors (synthesis markers) and plant sterols and cholestanol (absorption markers of cholesterol) reveals differences in cholesterol synthesis and absorption in the Finnish 4S subgroup divided in high triglyceride-low HDL cholesterol (lipid triad=HTG) and isolated high LDL cholesterol (ILDL) groups. Serum squalene and non-cholesterol sterol ratios to cholesterol were measured with gas-liquid chromatography at baseline, 6 weeks, 1 year, and 5 years on simvastatin. Patients with HTG (n=135) exhibited features of metabolic syndrome and, in spite of similar serum total and LDL cholesterol levels, ratios of synthesis markers were higher and those of absorption markers lower than in ILDL (n=133). The latter patients accumulated to a subgroup shown earlier to be clinical non-responders to simvastatin in 4S. Serum cholesterol reduction by simvastatin only tended to be higher in HTG than ILDL. The synthesis marker ratios were markedly reduced, and more effectively in HTG than ILDL, while the absorption marker ratios were increased, and for plant sterols more in ILDL than HTG. In conclusion, HTG is associated with high synthesis and low absorption of cholesterol, these events being opposite in ILDL. Synthesis is more effectively reduced by simvastatin in HTG than ILDL in spite of similar reduction in serum cholesterol. Patients defined by highest baseline absorption marker ratios in ILDL group are poor coronary event-reducers on regular simvastatin treatment.

摘要

我们假设,检测血清胆固醇前体(合成标志物)以及植物甾醇和胆甾烷醇(胆固醇吸收标志物),能够揭示芬兰4S研究亚组中高甘油三酯-低高密度脂蛋白胆固醇(脂质三联征=HTG)组和单纯高低密度脂蛋白胆固醇(ILDL)组在胆固醇合成和吸收方面的差异。在服用辛伐他汀的基线、6周、1年和5年时,采用气液色谱法测定血清角鲨烯和非胆固醇甾醇与胆固醇的比率。HTG组(n = 135)患者表现出代谢综合征的特征,尽管血清总胆固醇和低密度脂蛋白胆固醇水平相似,但与ILDL组(n = 133)相比,其合成标志物比率较高,吸收标志物比率较低。后一组患者聚集到一个先前在4S研究中显示对辛伐他汀临床无反应的亚组。辛伐他汀降低血清胆固醇的程度在HTG组仅略高于ILDL组。合成标志物比率显著降低,且在HTG组比在ILDL组降低得更有效,而吸收标志物比率升高,植物甾醇在ILDL组的升高幅度比在HTG组更大。总之,HTG与胆固醇的高合成和低吸收相关,这些情况在ILDL组中则相反。尽管血清胆固醇降低程度相似,但辛伐他汀在HTG组比在ILDL组更有效地降低了合成。在常规辛伐他汀治疗中,ILDL组中基线吸收标志物比率最高的患者对冠状动脉事件的降低效果较差。

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