我们先前已在社区动脉粥样硬化风险队列中的1,919名黑人中确定了2种循环次级胆汁酸(甘氨胆酸盐和硫酸糖脂巧克力)与房颤(AF)风险的关联。我们的目标是在社区参与者的2,003个白色和黑色动脉粥样硬化风险的独立样本中复制这些发现,并对3,922名参与者的合并样本进行了新的代谢组学分析,从1987年到2013年。使用气相和液相色谱质谱法在基线血清样品中进行代谢组学分析。根据心电图确定房颤,住院治疗,和死亡证明。我们使用多变量Cox回归通过代谢物水平的1个标准差来估计AF的风险比(HR)和95%置信区间(95CI)。在平均20年的随访中,608名参与者出现房颤。在复制和合并样本中,硫酸胆汁酸盐与AF相关(分别为HR1.10,95%CI1.00,1.21和HR1.13,95%CI1.04,1.22)。在复制样本中,硫酸葡萄糖巧克力与AF风险无关(HR1.02,95%CI0.92,1.13)。对组合队列中245种代谢物的分析确定了多重比较校正后与房颤相关的3种其他代谢物:假尿苷(HR1.18,95%CI1.10,1.28),尿苷(HR0.86,95%CI0.79,0.93)和刺梨(HR1.17,95%CI1.09,1.26)。总之,我们复制了先前鉴定的次级胆汁酸之间的前瞻性关联,硫酸甘胆酸酯,和AF发生率,并鉴定了参与核苷和多胺代谢的新代谢物作为AF风险的标志物。
We have previously identified associations of 2 circulating secondary bile acids (glycocholenate and glycolithocolate sulfate) with atrial fibrillation (AF) risk in 1,919 blacks in the Atherosclerosis Risk in Communities cohort. We aimed to replicate these findings in an independent sample of 2,003 white and black Atherosclerosis Risk in Communities participants, and performed a new metabolomic analysis in the combined sample of 3,922 participants, followed between 1987 and 2013. Metabolomic profiling was done in baseline serum samples using gas and liquid chromatography mass spectrometry. AF was ascertained from electrocardiograms, hospitalizations, and death certificates. We used multivariable Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of AF by 1 standard deviation difference of metabolite levels. Over a mean follow-up of 20 years, 608 participants developed AF. Glycocholenate sulfate was associated with AF in the replication and combined samples (HR 1.10, 95% CI 1.00, 1.21 and HR 1.13, 95% CI 1.04, 1.22, respectively). Glycolithocolate sulfate was not related to AF risk in the replication sample (HR 1.02, 95% CI 0.92, 1.13). An analysis of 245 metabolites in the combined cohort identified 3 additional metabolites associated with AF after multiple-comparison correction: pseudouridine (HR 1.18, 95% CI 1.10, 1.28), uridine (HR 0.86, 95% CI 0.79, 0.93) and acisoga (HR 1.17, 95% CI 1.09, 1.26). In conclusion, we replicated a prospective association among a previously identified secondary bile acid, glycocholenate sulfate, and AF incidence, and identified new metabolites involved in nucleoside and polyamine metabolism as markers of AF risk.