Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.
Associations between metabolomic compounds and incident heart failure among African Americans: the ARIC Study.
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DOI：
10.1093/aje/kwt004
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发表时间：
2013-08
影响因子：
5
通讯作者：
Yan Zheng;B. Yu;Danny C. Alexander;T. Manolio;D. Aguilar;J. Coresh;G. Heiss;E. Boerwinkle;J. Nettleton
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文献类型：
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作者：
Yan Zheng;B. Yu;Danny C. Alexander;T. Manolio;D. Aguilar;J. Coresh;G. Heiss;E. Boerwinkle;J. Nettleton
心力衰竭在非裔美国人中比在一般人群中更普遍。非裔美国人的代谢组学研究可以有效地识别心力衰竭的新生物标志物。我们使用非靶向方法测量了204种稳定的血清代谢物，并在中位随访20年后评估了它们与心力衰竭住院事件（n = 276）的相关性（1987-2008年），通过使用考克斯回归分析来自密西西比杰克逊的1,744名年龄在45-64岁且基线时无心力衰竭的非裔美国人的数据，社区动脉粥样硬化风险研究（ARIC）在调整已确定的风险因素后，我们发现16种代谢物（6种以已知结构身份命名，10种未命名，结构身份未知，后者使用格式X-12345表示）与心力衰竭事件相关（基于改良的Bonferroni程序，P < 0.0004）。在6种命名的代谢物中，4种参与氨基酸代谢，1种（脯氨酰羟脯氨酸）是二肽，1种（脯氨酰羟脯氨酸）是糖醇。在对肾功能进行额外校正后，2种代谢产物仍与心力衰竭事件相关（代谢产物X-11308，风险比= 0.75，95%置信区间：0.65，0.86;代谢产物X-11787，风险比= 1.23，95%置信区间：1.10，1.37）。进一步的结构分析显示X-11308是二羟基二十二碳三烯酸，X-11787是羟基亮氨酸或羟基异亮氨酸的同种型。我们的代谢组学分析揭示了与独立于传统危险因素的心力衰竭事件相关的新生物标志物。
Heart failure is more prevalent among African Americans than in the general population. Metabolomic studies among African Americans may efficiently identify novel biomarkers of heart failure. We used untargeted methods to measure 204 stable serum metabolites and evaluated their associations with incident heart failure hospitalization (n = 276) after a median follow-up of 20 years (1987-2008) by using Cox regression in data from 1,744 African Americans aged 45-64 years without heart failure at baseline from the Jackson, Mississippi, field center of the Atherosclerosis Risk in Communities (ARIC) Study. After adjustment for established risk factors, we found that 16 metabolites (6 named with known structural identities and 10 unnamed with unknown structural identities, the latter denoted by using the format X-12345) were associated with incident heart failure (P < 0.0004 based on a modified Bonferroni procedure). Of the 6 named metabolites, 4 are involved in amino acid metabolism, 1 (prolylhydroxyproline) is a dipeptide, and 1 (erythritol) is a sugar alcohol. After additional adjustment for kidney function, 2 metabolites remained associated with incident heart failure (for metabolite X-11308, hazard ratio = 0.75, 95% confidence interval: 0.65, 0.86; for metabolite X-11787, hazard ratio = 1.23, 95% confidence interval: 1.10, 1.37). Further structural analysis revealed X-11308 to be a dihydroxy docosatrienoic acid and X-11787 to be an isoform of either hydroxyleucine or hydroxyisoleucine. Our metabolomic analysis revealed novel biomarkers associated with incident heart failure independent of traditional risk factors.