Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study.
Metabolomics and Incidence of Atrial Fibrillation in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study.
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DOI：
10.1371/journal.pone.0142610
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Boerwinkle E
中科院分区：
文献类型：
--
作者：
Alonso A;Yu B;Qureshi WT;Grams ME;Selvin E;Soliman EZ;Loehr LR;Chen LY;Agarwal SK;Alexander D;Boerwinkle E
心房颤动（AF）是一种常见的心律失常。代谢组学方法可能识别疾病风险的新途径和生物标志物，但在房颤的纵向流行病学研究中的应用受到限制。我们通过非靶向代谢组学分析确定了118种血清代谢物与基线时无房颤的社区动脉粥样硬化风险研究（1987-1989）中1919名非裔美国男性和女性新诊断房颤发病率的前瞻性关联。通过研究心电图、出院代码和死亡证明确定2011年的AF病例。在中位22年的随访期间，我们确定了183例AF事件。在Cox比例风险模型中，校正了年龄、性别、吸烟、体重指数、收缩压、使用降压药、糖尿病、心力衰竭、冠心病和肾功能等因素后，两种共轭胆汁酸（硫酸乙醇胆酸酯和硫酸胆酸酯）与AF风险显著相关（p<0.0004）。多变量校正后的AF风险比（95%置信区间），每1个标准差以上的糖胆酸盐为1.22(1.12-1.32)，硫酸糖胆酸盐为1.22（1.10-1.35）。在额外调整酒精摄入量或循环白蛋白和肝酶浓度后，相关性没有明显差异。我们发现两种胆汁酸水平升高与房颤风险增加有关，指出了房颤发病机制的潜在新途径。独立研究结果的重复是有保证的。
Atrial fibrillation (AF) is a common arrhythmia. Application of metabolomic approaches, which may identify novel pathways and biomarkers of disease risk, to a longitudinal epidemiologic study of AF has been limited. We determined the prospective association of 118 serum metabolites identified through untargeted metabolomics profiling with the incidence of newly-diagnosed AF in 1919 African-American men and women from the Atherosclerosis Risk in Communities study without AF at baseline (1987–1989). Incident AF cases through 2011 were ascertained from study electrocardiograms, hospital discharge codes, and death certificates. During a median follow-up of 22 years, we identified 183 incident AF cases. In Cox proportional hazards models adjusted for age, sex, smoking, body mass index, systolic blood pressure, use of antihypertensive medication, diabetes, prevalent heart failure, prevalent coronary heart disease, and kidney function, two conjugated bile acids (glycolithocholate sulfate and glycocholenate sulfate) were significantly associated with AF risk after correcting for multiple comparisons (p<0.0004). Multivariable-adjusted hazard ratios (95% confidence intervals) of AF were 1.22 (1.12–1.32) for glycolithocholate sulfate and 1.22 (1.10–1.35) for glycocholenate sulfate per 1-standard deviation higher levels. Associations were not appreciably different after additional adjustment for alcohol consumption or concentrations of circulating albumin and liver enzymes. We found an association of higher levels of two bile acids with an increased risk of AF, pointing to a potential novel pathway in AF pathogenesis. Replication of results in independent studies is warranted.