Department of Internal Medicine I, Division of Cardiology, Pneumology, Angiology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University Jena, Germany.
Institute of Clinical Chemistry and Clinical Pharmacology, Medical Faculty, University of Bonn, Bonn, Germany.
Steroids. 2022 Nov;187:109079. doi: 10.1016/j.steroids.2022.109079. Epub 2022 Jul 11.
Blood cholesterol levels are regulated by competing mechanisms of cholesterol synthesis, absorption and excretion. Plant sterols are natural constituents of plants, are not synthesized in humans, and serve as markers for cholesterol absorption. Ezetimibe lowers the intestinal absorption of cholesterol and plant sterols. We analyzed the associations of differences in cholesterol metabolism, in particular increased cholesterol absorption, and the occurrence of in-stent restenosis (ISR) in patients with stable coronary artery disease.
Elective stent implantation of de novo stenosis was conducted in 59 patients (74.6 % males, 67.2 ± 9.6 years). Cholesterol and non-cholesterol sterols were quantified in serum samples by gas chromatography or mass spectrometry. ISR was assessed by optical coherence tomography (OCT) and quantitative angiography (QCA) after six months.
Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were positively associated with ISR measured by QCA (%diameter stenosis, late lumen loss) and OCT (proliferation volume, %area stenosis), whereas markers for cholesterol synthesis (e.g. lathosterol-to-cholesterol) were negatively associated with ISR (%area stenosis: r = -0.271, p = 0.043). There was no association between ISR and total cholesterol, LDL, HDL, triglycerides. Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were significantly lower in ezetimibe-treated patients compared to patients on a statin only (1.29 ± 0.69 vs. 2.22 ± 1.23; p = 0.007). Combined lipid-lowering with ezetimibe plus statin reduced ISR compared to statin only (13.7 ± 10.4 vs. 22.5 ± 12.1 %diameter stenosis, p = 0.015).
Differences in cholesterol metabolism, more specifically increased cholesterol absorption, are associated with ISR.
血液胆固醇水平受胆固醇合成、吸收和排泄的竞争机制调节。植物固醇是植物的天然成分，人体不能合成，可作为胆固醇吸收的标志物。依折麦布可降低肠道对胆固醇和植物固醇的吸收。我们分析了胆固醇代谢差异（特别是胆固醇吸收增加）与稳定型冠心病患者支架内再狭窄（ISR）发生的相关性。
对 59 例新发狭窄患者（74.6%为男性，67.2±9.6 岁）进行选择性支架植入。通过气相色谱或质谱法对血清样本中的胆固醇和非胆固醇甾醇进行定量。6 个月后，通过光学相干断层扫描（OCT）和定量血管造影（QCA）评估 ISR。
胆固醇吸收标志物（如谷固醇/胆固醇）与 QCA（%直径狭窄、晚期管腔丢失）和 OCT（增殖体积、%面积狭窄）测量的 ISR 呈正相关，而胆固醇合成标志物（如羊毛甾醇/胆固醇）与 ISR 呈负相关（%面积狭窄：r=-0.271，p=0.043）。ISR 与总胆固醇、LDL、HDL、甘油三酯均无相关性。与他汀类药物治疗的患者相比，依折麦布治疗的患者胆固醇吸收标志物（如谷固醇/胆固醇）明显降低（1.29±0.69 比 2.22±1.23；p=0.007）。与仅用他汀类药物治疗相比，依折麦布联合他汀类药物降脂可降低 ISR（13.7±10.4%比 22.5±12.1%直径狭窄，p=0.015）。
胆固醇代谢的差异，更具体地说是胆固醇吸收的增加，与 ISR 相关。
