Yoshino Satoshi, Hamasaki Shuichi, Ishida Sanemasa, Kataoka Tetsuro, Yoshikawa Akiko, Oketani Naoya, Saihara Keishi, Ichiki Hitoshi, Kuwahata So, Fujita Shoji, Takumi Takuro, Yoshimoto Issei, Nakazaki Mitsuhiro, Tei Chuwa
Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Heart Vessels. 2013 Mar;28(2):157-65. doi: 10.1007/s00380-011-0228-z. Epub 2012 Mar 29.
Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.
胆红素可防止低密度脂蛋白（LDL）氧化，并可能预防动脉粥样硬化和冠心病（CHD）。本研究的目的是通过测量胆红素浓度、冠状动脉内皮功能以及氧化应激、炎症和脂质/葡萄糖代谢的标志物，来描述胆红素与冠心病之间的关系。研究人群包括141例未患冠心病且接受了多普勒血流研究的患者。使用多普勒导丝通过冠状动脉内注射罂粟碱、乙酰胆碱（ACh）和硝酸甘油来检查血管反应性。还测量了血清胆红素、高敏C反应蛋白（hsCRP）、丙二醛修饰的LDL、LDL胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、空腹血糖（FPG）和免疫反应性胰岛素。计算了稳态模型评估胰岛素抵抗指数和估计肾小球滤过率（eGFR）。单因素分析显示，ACh诱导的冠状动脉血流（CBF）百分比变化和冠状动脉直径均与对数转换后的胆红素呈正相关（分别为r = 0.22，P < 0.05；r = 0.20，P < 0.05）。ACh刺激后CBF的百分比变化与eGFR呈正相关（r = 0.24，P < 0.05），与年龄、LDL-C和对数转换后的FPG呈负相关（分别为r = -0.24，P < 0.05；r = -0.17，P < 0.05，r = -0.22，P < 0.05）。多因素分析显示，对数转换后的胆红素是ACh刺激后CBF百分比变化的唯一独立预测因子。多因素分析显示，对数转换后的hsCRP和HDL-C是对数转换后胆红素的独立预测因子。这些结果表明，高水平的胆红素与良好的冠状动脉内皮功能相关，这可能是通过胆红素对炎症和HDL-C的作用介导的。
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