Twickler T B, Dallinga-Thie G M, de Valk H W, Schreuder P C, Jansen H, Cabezas M C, Erkelens D W
Department of Cardiovascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2422-7. doi: 10.1161/01.atv.20.11.2422.
Familial hypercholesterolemia (FH) and disturbances in postprandial lipoprotein metabolism are both associated with premature atherosclerosis. The effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors on plasma cholesterol levels in patients with FH is well established; however, it is not known whether postprandial lipoproteins are also influenced. In this case-controlled intervention study, we investigated the effects of high-dose simvastatin on postprandial lipoproteins. We used a new method to analyze remnant lipoproteins based on the immunoseparation principle (remnant-like particle cholesterol [RLP-C] assay) and the well-established measurement of retinyl ester (RE) analysis in plasma and in the Svedberg flotation unit (Sf)<1000 fraction. Seven heterozygous FH patients and 7 control subjects matched for sex, age, body mass index, triglycerides, and apolipoprotein E genotype were enrolled in the study. An oral vitamin A (RE) fat-loading test was performed at baseline in both groups and after 3 months of high-dose simvastatin (80 mg/d) treatment in the FH patients. Before treatment, FH patients had significantly higher fasting and postprandial concentrations of lipoprotein remnants (plasma RLP-C 42+/-19 mg/dL and area under the RLP-C curve 415+/-82 mg. L(-1). h(-1), respectively) than did control subjects (7+/-3 mg/dL and 101+/-35 mg. L( -1). h(-1), respectively; P<0.05), suggesting a delayed clearance of chylomicron remnant particles in the FH patients. Treatment with simvastatin significantly reduced fasting and postprandial remnant lipoprotein cholesterol concentrations (13+/-3 mg/dL and 136+/-53 mg. L(-1). h(-1), respectively; P<0.05 for both). Postprandial RE in the Sf<1000 fraction, not total RE in plasma, was also significantly higher in FH patients than in control subjects (24+/-10 versus 6.3+/-5.9 mg. L( -1). h(-1), P<0.05), but treatment with simvastatin did not result in improvement of the postprandial RE response, either in the Sf<1000 fraction or in plasma. It is concluded that heterozygous FH patients have increased fasting and postprandial remnant lipoprotein concentrations. Treatment with simvastatin significantly reduced the fasting and postprandial RLP-C concentrations but did not result in improved postprandial RE response.
家族性高胆固醇血症（FH）和餐后脂蛋白代谢紊乱均与早发性动脉粥样硬化相关。β-羟基-β-甲基戊二酰辅酶A还原酶抑制剂对FH患者血浆胆固醇水平的影响已得到充分证实；然而，尚不清楚其是否也会影响餐后脂蛋白。在这项病例对照干预研究中，我们调查了大剂量辛伐他汀对餐后脂蛋白的影响。我们采用了一种基于免疫分离原理的新方法来分析残余脂蛋白（类残余颗粒胆固醇[RLP-C]测定法），并采用了成熟的血浆和Svedberg漂浮单位（Sf）<1000组分中视黄醇酯（RE）分析测量方法。七名杂合子FH患者和七名在性别、年龄、体重指数、甘油三酯和载脂蛋白E基因型方面相匹配的对照受试者被纳入研究。两组在基线时均进行了口服维生素A（RE）脂肪负荷试验，FH患者在接受3个月大剂量辛伐他汀（80mg/d）治疗后再次进行该试验。治疗前，FH患者空腹和餐后脂蛋白残余物浓度（血浆RLP-C分别为42±19mg/dL和RLP-C曲线下面积为415±82mg·L⁻¹·h⁻¹）显著高于对照受试者（分别为7±3mg/dL和101±35mg·L⁻¹·h⁻¹；P<0.05），提示FH患者乳糜微粒残余颗粒清除延迟。辛伐他汀治疗显著降低了空腹和餐后残余脂蛋白胆固醇浓度（分别为13±3mg/dL和136±53mg·L⁻¹·h⁻¹；两者P均<0.05）。FH患者Sf<1000组分中的餐后RE，而非血浆中的总RE，也显著高于对照受试者（24±10对6.3±5.9mg·L⁻¹·h⁻¹，P<0.05），但辛伐他汀治疗并未改善Sf<1000组分或血浆中的餐后RE反应。结论是，杂合子FH患者空腹和餐后残余脂蛋白浓度升高。辛伐他汀治疗显著降低了空腹和餐后RLP-C浓度，但并未改善餐后RE反应。
