Objective: To explore the associations of plasma acylcarnitine and bile acid levels with the risk of incident coronary heart disease (CHD) in Chinese adults. Methods: The baseline survey of China Kadoorie Biobank (CKB) took place in 10 areas across China during 2004-2008, and the first resurvey took place from July to October 2008, with collection of data via questionnaire, physical examination and blood samples. The current study was based on 2 159 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of CKB. The associations of acylcarnitines and bile acids with incident CHD were assessed using Cox proportional hazards regression models. Unweighted metabolites scores were constructed to assess the overall effect of acylcarnitines and bile acids on incident CHD. The impact of metabolites on the performance of CHD prediction model was evaluated with the receiver operating characteristic (ROC) area under the curve (AUC). Follow-up for CHD incidence was censored on December 31, 2018. Results: The mean age of the participants was (53.1±9.8) years and 754 were males (34.9%). During (10.5±0.1) years of follow-up, 140 cases of CHD were recorded. Four metabolites including acylcarnitines C3-OH, C5:1, C5:1-DC, and deoxycholic acid (DCA) showed associations with CHD incidence and the HR (95%CI) were 1.474 (1.230-1.767), 0.761 (0.637-0.909), 0.773 (0.650-0.918), and 1.309 (1.113-1.539), respectively [false discovery rate (FDR)0.05]. All metabolite scores, including short-chain, medium-chain, long-chain acylcarnitines, primary and secondary bile acids scores were associated with the risk of CHD (FDR0.05). Compared to the traditional models, the addition of DCA or 4 key metabolites increased the AUC of the predictive model from 0.803 (0.761-0.845) to 0.812 (0.772-0.852) and 0.817 (0.778-0.857), respectively (all P0.05). Conclusions: Acylcarnitine and bile acid levels are associated with the risk of CHD, and DCA or 4 key metabolites can improve the predictive ability for CHD incidence.
目的： 探索中国成年人血浆酰基肉碱和胆汁酸水平与冠心病（CHD）发病风险的关联。 方法： 中国慢性病前瞻性研究（CKB）于2004—2008年在中国10个地区开展基线调查，并于2008年7—10月开展第1次重复调查，2次调查内容均包括问卷调查、体格检查和血液样本采集。本研究基于CKB项目第1次重复调查中具有血浆靶向质谱代谢组数据的2 159名研究对象数据，对代谢物浓度进行基于秩的逆正态转换后，采用Cox比例风险回归模型分析血浆中40种酰基肉碱和14种胆汁酸与CHD发病风险的关联。同时，在两类代谢物中分别构建代谢物评分，评估不同类别代谢物与CHD发病关联的整体效应。采用受试者工作特征（ROC）曲线下面积（AUC）评价代谢物对CHD预测模型预测能力的提升效果。随访时间截至2018年12月31日。 结果： 研究对象年龄（53.1±9.8）岁，男754名（34.9%）。随访时间（10.5±0.1）年，期间确诊新发CHD 140例。单一代谢物分析结果显示，酰基肉碱C3-OH、C5∶1、C5∶1-DC和去氧胆酸（DCA）与CHD发生有关联［错误发现阳性率（FDR）0.05，HR值（95%CI）分别为1.474（1.230~1.767）、0.761（0.637~0.909）、0.773（0.650~0.918）和1.309（1.113~1.539）］。各类代谢物评分，包括短链、中链、长链酰基肉碱和初级、次级胆汁酸评分均与CHD发病风险相关（均FDR0.05）。与传统预测模型相比，加入DCA或4个关键代谢物的模型AUC（95%CI）由0.803（0.761~0.845）分别提高至0.812（0.772~0.852）和0.817（0.778~0.857）（均P0.05）。 结论： 酰基肉碱及胆汁酸水平与CHD发病风险有关，DCA或4个关键代谢物能够提高对CHD发病风险的预测能力。.