Statins but not fibrates improve the atherogenic to anti-atherogenic lipoprotein particle ratio: a randomized crossover study.

Sammy Y Chan, G B John Mancini, Andrew Ignaszewski, Jiri Frohlich
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引用次数: 8

Abstract

Background: Prior studies suggested low density lipoprotein particle (LDLP) size is a predictor of atherosclerosis. Knowledge of effects of lipid lowering drugs on lipoprotein subclasses is useful. We treated subjects with hyperlipidemia sequentially with statins and fibrates, the 2 main classes of lipid lowering therapy and studied changes in NMR lipoprotein subclasses.

Methods: 35 subjects (21 males; 60 +/- 12 y) were enrolled in a crossover study. Subjects had baseline lipid profile & apoB. Lipoprotein subclasses, particle numbers and diameters were assessed with NMR spectroscopy. Subjects were randomized to simvastatin 20 mg or fenofibrate 200 mg. Repeat testing was done at 12 weeks. After 6 week washout, subjects were started on alternate drug for 12 weeks with pre/post tests.

Results: Both therapies resulted in expected changes in lipids and apoB. Decreases in total cholesterol, LDL and apoB were greater with simvastatin. Fenofibrate led to small increase in HDL. Both therapies decreased LDLP. Reduction in LDLP was greater with simvastatin (32%, p < .001) compared to fenofibrate (17%; p = .036 vs pre; p = .027 vs simvastatin end). Fenofibrate resulted in 17% rise in large LDLP (p = .06 vs pre) and 32% drop in small LDLP (p = .007 vs pre). Simvastatin led to decrease in both LDLP fractions (19% large LDLP; p = .001 vs fenofibrate end; 34% small LDLP, p = .019 vs pre). With fenofibrate, LDLP size increased from 20.4 nm to 20.8 nm (p = .037). There was no change in LDLP size with simvastatin. There was 18% increase in HDL particle number (HDLP) with fenofibrate (p = .05). There were no changes in HDLP with simvastatin. There were no changes in HDLP size with either drug. Pre- and post-therapy LDLP/HDLP ratio was similar with fenofibrate but was reduced by simvastatin (p = .045).

Conclusion: Simvastatin reduced LDLP across all subclasses with no effect on size. Simvastatin had no effect on HDLP. Fenofibrate had weak effect on LDLP number but increased LDLP size by raising large LDLP and reducing small LDLP. Fenofibrate had weak effect on HDLP number with no change in size. Importantly, net atherogenic to antiatherogenic lipoprotein ratio (LDLP/HDLP) was reduced by simvastatin but not by fenofibrate.

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他汀类药物而非贝特类药物改善致动脉粥样硬化与抗动脉粥样硬化脂蛋白颗粒比率:一项随机交叉研究。
背景:先前的研究表明低密度脂蛋白颗粒(LDLP)大小是动脉粥样硬化的一个预测因子。了解降脂药物对脂蛋白亚类的影响是有用的。我们依次用他汀类药物和贝特类药物治疗高脂血症患者,并研究了核磁共振脂蛋白亚类的变化。方法:35例受试者(男性21例;60名+/- 12名患者被纳入交叉研究。受试者有基线血脂和载脂蛋白。用核磁共振光谱法测定脂蛋白亚类、颗粒数和直径。受试者被随机分配到辛伐他汀20 mg或非诺贝特200 mg。12周时重复检测。6周洗脱期后,受试者开始使用替代药物12周,并进行前后测试。结果:两种治疗均可导致血脂和载脂蛋白的预期变化。辛伐他汀组总胆固醇、低密度脂蛋白和载脂蛋白降低幅度更大。非诺贝特导致HDL的小幅增加。两种疗法均可降低ldl。辛伐他汀组ldl降低率(32%,p < 0.001)高于非诺贝特组(17%;P = 0.036 vs前;P = 0.027 vs辛伐他汀终点)。非诺贝特导致大ldl升高17% (p = 0.06 vs前),小ldl下降32% (p = 0.07 vs前)。辛伐他汀导致两组ldl分数下降(19%大ldl;P = 0.001 vs非诺贝特组;34%小LDLP, p = 0.019 vs前)。非诺贝特组LDLP尺寸从20.4 nm增加到20.8 nm (p = 0.037)。辛伐他汀治疗后ldl大小没有变化。非诺贝特组HDL颗粒数(HDLP)增加18% (p = 0.05)。辛伐他汀组HDLP无变化。两种药物均未改变HDLP的大小。治疗前和治疗后ldl /HDLP比值与非诺贝特相似,但辛伐他汀降低(p = 0.045)。结论:辛伐他汀降低了所有亚类的LDLP,对大小没有影响。辛伐他汀对HDLP无影响。非诺贝特对低密度脂蛋白数量的影响较弱,但对低密度脂蛋白大小的影响较大,可以提高低密度脂蛋白的数量,降低低密度脂蛋白的数量。非诺贝特对HDLP数量影响较弱,对HDLP大小无影响。重要的是,辛伐他汀降低了致动脉粥样硬化与抗动脉粥样硬化的净脂蛋白比率(LDLP/HDLP),而非诺贝特没有降低。
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