BACKGROUND & AIMS:
OBJECTIVE:To assess whether an abnormality in cholesterol absorption or synthesis may be associated with hypocholesterolemia in patients with single ventricle anatomy following Fontan palliation.
STUDY DESIGN:This is a cross-sectional study of 21 patients with hypocholesterolemia following Fontan procedure and age/sex-matched healthy controls, with median age of 13.4 (IQR 10.6-16.1) years. Laboratory values of several biomarkers, including phytosterols and 5-α-cholestanol (for cholesterol absorption) and lathosterol (for cholesterol biosynthesis), as well as cholesterol levels, inflammatory markers, and indices of liver function were compared between patients following Fontan procedure and controls.
RESULTS:The Fontan cohort had significantly lower total cholesterol (mean 117 ± SD 13.9, vs 128 ± 19.2 mg/dL, P = .03) and free cholesterol (35.5 ± 4.5 vs 39.2 ± 5.4 mg/dL, P = .02) compared with control patients. There was an increase in normalized 5-α-cholestanol (1.51 ± 0.6 vs 1.14 ± 0.37 μg/mL, P = .02), and a significantly lower lathosterol/5-α-cholestanol ratio (0.70 ± 0.38 vs 1.11 ± 0.76, P = .04). There was a strong correlation (r = 0.78, P < .0001) between lathosterol and cholesterol levels in the Fontan cohort, not seen in controls (r = 0.47, P = .04). The Fontan cohort also had significantly higher C-reactive protein, transaminases, total bilirubin, and gamma-glutamyl transferase levels.
CONCLUSIONS:Patients with hypocholesterolemia following Fontan procedure have evidence of increased cholesterol absorption and decreased cholesterol synthesis. As cholesterol absorption efficiency is a regulated process, this finding suggests an upregulation of cholesterol absorption as a result of decreased cholesterol production. In the setting of elevated liver indices and possible inflammation, this finding supports a growing body of data suggesting development of liver disease in patients receiving Fontan.
背景与目标:
目的:评估单侧解剖后方丹心律减退的患者胆固醇吸收或合成异常是否与低胆固醇血症有关。
研究设计:这是一项横断面研究,涉及21例接受Fontan手术和年龄/性别匹配的健康对照的低胆固醇血症患者,中位年龄为13.4岁(IQR 10.6-16.1)岁。在Fontan程序和对照组之间比较了一些生物标志物的实验室值,包括植物甾醇和5-α-胆固醇(用于胆固醇吸收)和谷甾醇(用于胆固醇生物合成),以及胆固醇水平,炎症标志物和肝功能指标。 。
结果:丰坦队列的总胆固醇显着降低(平均117±SD 13.9,vs 128±19.2 mg / dL,P = .03)和游离胆固醇(35.5±4.5 vs 39.2±5.4 mg / dL,P = .02)与对照患者相比。标准化的5-α-胆固醇的增加(1.51±0.6比1.14±0.37μg/ mL,P = .02),谷甾醇/5-α-胆固醇的比率显着降低(0.70±0.38比1.11±0.76, P = .04)。在丰坦队列中,谷甾醇与胆固醇水平之间存在很强的相关性(r = 0.78,P <.0001),而在对照组中则没有(r = 0.47,P = .04)。 Fontan队列还具有显着较高的C反应蛋白,转氨酶,总胆红素和γ-谷氨酰转移酶水平。
结论:丰坦手术后患有低胆固醇血症的患者有证据表明胆固醇吸收增加,胆固醇合成减少。由于胆固醇吸收效率是一个受调节的过程,因此该发现表明由于胆固醇生成减少,胆固醇吸收上调。在肝指数升高和可能发炎的情况下,这一发现支持了越来越多的数据,表明接受Fontan的患者出现肝病。