Otto C, Parhofer K G, Ritter M M, Richter W O, Schwandt P
Medical Department II, Klinikum Grosshadern, University of Munich, Germany.
Br J Clin Pharmacol. 1998 Nov;46(5):473-8. doi: 10.1046/j.1365-2125.1998.00816.x.
Epidemiological data have shown that haemorheological disorders are associated with an increased risk of atherosclerosis. We evaluated the effect of the nicotinic acid derivative acipimox on haemorheological and lipid parameters in 18 patients with mixed hyperlipoproteinaemia using a randomized, double-blind, placebo-controlled, cross-over study protocol.
Patients (7 women, 11 men, aged 49.3+/-3.0 years) were investigated with acipimox (dose adjusted to weight, 500 or 750 mg daily) compared with placebo treatment each for 12 weeks. Lipid parameters, whole blood viscosity, plasma viscosity, fibrinogen, and red cell aggregation at native and standardized (0.45) haematocrit as well as red cell filterability were measured at baseline, at week 12 (change of therapy), and at week 24.
Total cholesterol concentration (8.30+/-0.32 vs 8.72+/-0.36 mmol/l(-1)) and apolipoprotein B (198.5+/-9.9 vs 217+/-9.9 mg dl(-1)) were significantly lower (P<0.05) during acipimox therapy compared with placebo, no significant changes were observed for triglycerides and low-density lipoprotein [LDL] cholesterol. However, total high-density lipoprotein [HDL] cholesterol (1.24+/-0.05 vs 1.10+/-0.05 mmol l(-1), P<0.001) as well as HDL2 and HDL3 cholesterol (P<0.05) were significantly higher during acipimox therapy. The LDL cholesterol to HDL cholesterol ratio significantly improved during acipimox therapy (4.63+/-0.25 vs 5.49+/-0.26, P<0.001). Red cell aggregation at native and standardized haematocrit were the only haemorheological parameters which improved during acipimox therapy in comparison with placebo (shear rate 3 s(-1):10.69+/-0.40 vs 11.50+/-0.44 U, P<0.05, for native red cell aggregation; 10.40+/-0.36 vs 11.28+/-0.39 U, P<0.05, for standardized red cell aggregation).
We conclude, that the cardiovascular risk profile improves during acipimox therapy due to an elevation in HDL cholesterol and its subfractions as well as a decrease in red cell aggregation.
流行病学数据表明，血液流变学紊乱与动脉粥样硬化风险增加相关。我们采用随机、双盲、安慰剂对照、交叉研究方案，评估了烟酸衍生物阿西莫司对18例混合性高脂蛋白血症患者血液流变学和血脂参数的影响。
对患者（7名女性，11名男性，年龄49.3±3.0岁）进行研究，将阿西莫司（剂量根据体重调整，每日500或750毫克）与安慰剂治疗各进行12周对比。在基线、第12周（治疗改变时）和第24周测量血脂参数、全血粘度、血浆粘度、纤维蛋白原，以及在自然和标准化（0.45）血细胞比容下的红细胞聚集情况和红细胞滤过率。
与安慰剂相比，阿西莫司治疗期间总胆固醇浓度（8.30±0.32对8.72±0.36毫摩尔/升（-1））和载脂蛋白B（198.5±9.9对217±9.9毫克/分升（-1））显著降低（P<0.05），甘油三酯和低密度脂蛋白[LDL]胆固醇未观察到显著变化。然而，阿西莫司治疗期间总高密度脂蛋白[HDL]胆固醇（1.24±0.05对1.10±0.05毫摩尔/升，P<0.001）以及HDL2和HDL3胆固醇（P<0.05）显著升高。阿西莫司治疗期间LDL胆固醇与HDL胆固醇的比值显著改善（4.63±0.25对5.49±0.26，P<0.001）。与安慰剂相比，在自然和标准化血细胞比容下的红细胞聚集是阿西莫司治疗期间唯一改善的血液流变学参数（切变率3秒（-1）：自然红细胞聚集为10.69±0.40对11.50±0.44单位，P<0.05；标准化红细胞聚集为10.40±0.36对11.28±0.39单位，P<0.05）。
我们得出结论，在阿西莫司治疗期间，由于HDL胆固醇及其亚组分升高以及红细胞聚集减少，心血管风险状况得到改善。
