Franceschini G, Cassinotti M, Vecchio G, Gianfranceschi G, Pazzucconi F, Murakami T, Sirtori M, D'Acquarica A L, Sirtori C R
Center E. Grossi Paoletti, University of Milano, Italy.
Arterioscler Thromb. 1994 Oct;14(10):1569-75. doi: 10.1161/01.atv.14.10.1569.
Familial combined hyperlipidemia (FCHL) is the most common genetic lipid disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the high coronary risk of FCHL patients. We investigated the ability of pravastatin to favorably correct plasma lipid and lipoprotein levels and LDL structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL cholesterol levels by 21% and 32%, respectively. Triglyceride levels did not change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% because of a significant 73% rise of HDL2 cholesterol. LDL were smaller (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholesteryl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control subjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB (cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatment. Although pravastatin favorably altered plasma lipid and lipoprotein levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of the small, dense LDL to drug-induced modifications, a maximal lipid-lowering effect is needed to reduce coronary risk in FCHL patients.
家族性混合型高脂血症（FCHL）是心肌梗死年轻幸存者中最常见的遗传性脂质紊乱疾病。血浆总胆固醇和低密度脂蛋白（LDL）胆固醇升高以及小而密LDL颗粒的患病率均与FCHL患者的高冠状动脉风险有关。我们研究了普伐他汀对FCHL患者血浆脂质和脂蛋白水平以及LDL结构进行有利校正的能力。通过对一级亲属的研究记录确诊的12例FCHL患者接受普伐他汀（40mg/d）治疗12周。普伐他汀使血浆总胆固醇和LDL胆固醇水平分别显著降低了21%和32%。甘油三酯水平未发生变化，载脂蛋白B（apoB）浓度降低了9%（P=无显著性差异）。高密度脂蛋白（HDL）胆固醇升高了6%，这是由于HDL2胆固醇显著升高了73%。与家族性高胆固醇血症患者或健康对照受试者相比，所选患者的LDL较小（直径为24.5±0.5nm）、浮力较小且富含apoB（胆固醇酯-apoB比值为1.64±0.46）。普伐他汀治疗后，LDL变得更小（23.8±0.6nm）且apoB含量更高（胆固醇酯-apoB比值为1.27±0.52）。尽管普伐他汀对FCHL患者的血浆脂质和脂蛋白水平产生了有利改变，但异常的LDL颗粒分布和组成并未受到影响。由于小而密LDL对药物诱导修饰具有明显抗性，因此需要最大程度地降低血脂以降低FCHL患者的冠状动脉风险。
