Department of Internal Medicine, Hopital de Jolimont, Haine Saint Paul, Belgium.
Atherosclerosis. 2011 Aug;217(2):308-21. doi: 10.1016/j.atherosclerosis.2011.06.010. Epub 2011 Jun 12.
The evidence of the different concepts underlying the interplay between cholesterol absorption and synthesis in the context of statin and ezetimibe treatment were reviewed in the light of the eight major trials where cholesterol absorption and synthesis were analyzed on a large scale using the plasma levels of precursors of cholesterol and plant sterols. The only concept supported in all studies is a significant and consistent increase of cholesterol absorption with statin (correlated with the inhibition of synthesis) and of cholesterol synthesis with ezetimibe, whereas in combination, statin and ezetimibe reduce both cholesterol synthesis and absorption. In contrast, most of the other concepts failed to be clearly proven. At baseline, the inverse relationship between cholesterol absorption and synthesis (only examined in two studies) was found to be weak. On statin treatment, four studies showed that the changes in cholesterol synthesis and absorption, contributed less than 9% to the variability in cholesterol response to statin therapy. It has not been consistently demonstrated that good absorbers/bad synthesizers are bad responders to statin (6 studies) and good responders for ezetimibe (3 studies). There is also no clear inverse correlation between LDL reduction on statin treatment and that on ezetimibe treatment. Finally, the original idea from the first pioneer study of Miettinen et al. that, the higher the baseline intestinal ability to absorb cholesterol, the lower the benefit on the clinical cardiovascular outcomes was not reproduced in the PROSPER study. In conclusion, with the exception of a reverse effect of statin and ezetimibe on absorption and synthesis, most ideas supporting the interplay between cholesterol absorption and synthesis lacked consistency between studies. At present, the use of the plasma levels of plant sterols and cholesterol precursors as markers of cholesterol absorption and synthesis is far too limited to definitively solve these questions.
基于他汀类药物和依折麦布治疗时胆固醇吸收和合成相互作用的不同概念的证据，根据使用胆固醇前体和植物固醇的血浆水平大规模分析胆固醇吸收和合成的八项主要试验进行了综述。所有研究都支持的唯一概念是，他汀类药物（与合成抑制相关）显著且一致地增加胆固醇吸收，依折麦布增加胆固醇合成，而联合使用他汀类药物和依折麦布则降低胆固醇合成和吸收。相比之下，其他大多数概念都未能得到明确证明。在基线时，胆固醇吸收和合成之间的反相关关系（仅在两项研究中进行了检查）被发现很弱。在他汀类药物治疗时，四项研究表明，胆固醇合成和吸收的变化对他汀类药物治疗的胆固醇反应的变异性的贡献小于 9%。尚未一致证明良好吸收者/不良合成者对他汀类药物（6 项研究）反应差，对依折麦布（3 项研究）反应好。他汀类药物治疗时 LDL 降低与依折麦布治疗时 LDL 降低之间也没有明显的负相关关系。最后，Miettinen 等人的第一项先驱研究的原始想法是，基线时肠道吸收胆固醇的能力越高，临床心血管结局的获益就越低，但在 PROSPER 研究中并没有重现这一观点。总之，除了他汀类药物和依折麦布对吸收和合成的反向作用外，大多数支持胆固醇吸收和合成相互作用的概念在研究之间缺乏一致性。目前，使用植物固醇和胆固醇前体的血浆水平作为胆固醇吸收和合成的标志物还远远不能明确解决这些问题。
