代谢酶表型可能会影响他汀类药物对降低冠心病患者小而密低密度脂蛋白胆固醇的疗效。
metabolizer phenotypes may affect the efficacy of statins on lowering small dense low-density lipoprotein cholesterol of patients with coronary artery disease.
作者信息
Dai Ruozhu, Zhao Xiaoyu, Zhuo Huilin, Wang Wei, Xu Yue, Hu Zixin, Zhang Tiexu, Zhao Jiangman
机构信息
Department of Cardiology, Quanzhou First Hospital Afliated to Fujian Medical University, Quanzhou, Fujian, China.
Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, China.
出版信息
Front Cardiovasc Med. 2022 Dec 19;9:1016126. doi: 10.3389/fcvm.2022.1016126. eCollection 2022.
BACKGROUND
Dyslipidemia is a major cause of arteriosclerotic cardiovascular disease (ASCVD), and low-density lipoprotein cholesterol (LDL-C) is the profile to be reduced to prevent disease progression. Small dense low-density lipoprotein cholesterol (sdLDL-C) has been proven to be a more effective biomarker than LDL-C for ASCVD primary and secondary prevention. is an important drug metabolism gene. This study aimed to investigate the relationship between sdLDL-C and coronary artery disease (CAD) risk factors and explore the influence of metabolizer phenotypes on the sdLDL-C lowering efficacy of statins.
METHODS
This study recruited 182 patients with CAD and 200 non-CAD controls. Baseline laboratory indices of fasting blood were detected, including blood lipids, glucose, and creatinine. In addition, LDL-C subfractions were separated and quantified. Gene polymorphisms of and were detected in patients with CAD. The LDL-C subfractions levels of patients with CAD were followed up after statin drug treatment.
RESULTS
Total cholesterol, LDL-C, LDLC-2, LDLC-3, LDLC-4, LDLC-5, LDLC-6, LDLC-7, and sdLDL-C levels of patients with CAD were significantly higher than those in non-CAD controls. Meanwhile, sdLDL-C (AUC = 0.838) and LDLC-4 (AUC = 0.835) performed outstandingly in distinguishing patients with CAD from controls. Based on metabolizer phenotypes, 113 patients with CAD were divided into the extensive metabolizer (EM, = 49), intermediate metabolizer (IM, = 52), and poor metabolizer (PM, = 12) groups. The patients with IM and PM metabolizer phenotypes had better sdLDL-C lowering efficacy after taking statin drugs than patients with EM phenotype ( = 0.0268, FDR = 0.0536). The genotype had no significant impact on the efficacy of statins ( = 0.1611, FDR = 0.1611).
CONCLUSION
sdLDL-C and LDLC-4 outperformed other blood lipids such as LDL-C for CAD risk screening. metabolizer phenotypes had the potential to predict the efficacy of statins in lowering sdLDL-C.
背景
血脂异常是动脉粥样硬化性心血管疾病（ASCVD）的主要病因，低密度脂蛋白胆固醇（LDL-C）是需要降低以预防疾病进展的指标。小而密低密度脂蛋白胆固醇（sdLDL-C）已被证明是比LDL-C更有效的ASCVD一级和二级预防生物标志物。[具体基因名称]是一个重要的药物代谢基因。本研究旨在探讨sdLDL-C与冠状动脉疾病（CAD）危险因素之间的关系，并探讨[具体基因名称]代谢者表型对他汀类药物降低sdLDL-C疗效的影响。
方法
本研究招募了182例CAD患者和200例非CAD对照。检测空腹血的基线实验室指标，包括血脂、血糖和肌酐。此外，分离并定量LDL-C亚组分。在CAD患者中检测[具体基因名称]和[具体基因名称]的基因多态性。对CAD患者进行他汀类药物治疗后的LDL-C亚组分水平进行随访。
结果
CAD患者的总胆固醇、LDL-C、LDLC-2、LDLC-3、LDLC-4、LDLC-5、LDLC-6、LDLC-7和sdLDL-C水平显著高于非CAD对照。同时，sdLDL-C（AUC = 0.838）和LDLC-4（AUC = 0.835）在区分CAD患者和对照方面表现出色。根据[具体基因名称]代谢者表型，113例CAD患者分为广泛代谢者（EM，n = 49）、中间代谢者（IM，n = 52）和慢代谢者（PM，n = 12）组。IM和PM代谢者表型的患者服用他汀类药物后sdLDL-C降低疗效优于EM表型患者（P = 0.0268，FDR = 0.0536）。[具体基因名称]基因型对他汀类药物疗效无显著影响（P = 0.1611，FDR = 0.1611）。
结论
在CAD风险筛查中，sdLDL-C和LDLC-4比其他血脂如LDL-C表现更优。[具体基因名称]代谢者表型有可能预测他汀类药物降低sdLDL-C的疗效。
Zotero 插件