Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers.
Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers.
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DOI：
10.1136/heartjnl-2016-310789
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Peters A
中科院分区：
文献类型：
--
作者：
Ward-Caviness CK;Xu T;Aspelund T;Thorand B;Montrone C;Meisinger C;Dunger-Kaltenbach I;Zierer A;Yu Z;Helgadottir IR;Harris TB;Launer LJ;Ganna A;Lind L;Eiriksdottir G;Waldenberger M;Prehn C;Suhre K;Illig T;Adamski J;Ruepp A;Koenig W;Gudnason V;Emilsson V;Wang-Sattler R;Peters A
低分子量化合物的综合分析（例如代谢组学）提供了一种独特的工具来发现新的生物标志物并了解心肌梗死 (MI) 的潜在途径。我们使用靶向代谢组学方法来识别 MI 生物标志物并评估它们在 MI 发病机制中的参与。使用三个独立的前瞻性队列（KORA S4、KORA S2 和 AGES-REFINE），总共 2257 名基线时没有 MI 病史的参与者，我们确定了与 MI 事件相关的代谢物（266 例）。我们还研究了代谢物与高敏 C 反应蛋白 (hsCRP) 之间的关联，以了解这些代谢物与全身炎症之间的关系。在 140 种代谢物中，有 16 种代谢物名义上与 KORA S4 中的 MI 事件相关（p<0.05）。三种代谢物，精氨酸和两种溶血磷脂酰胆碱（LPC 17:0 和 LPC 18:2），通过 KORA S4 中的向后逐步选择程序被选为生物标志物，并且在包括 KORA S2 和 AGES-REFINE 在内的所有三项研究的荟萃分析中具有显着性（p<0.0003）。此外，这三种代谢物增加了 Framingham 风险评分的预测价值，增加了 KORA S4（从 0.70 至 0.78，p=0.001）和 AGES-REFINE 研究（从 0.70 至 0.76，p=0.02）中受试者操作特征评分下的面积，但在 KORA S2 中未观察到。代谢物生物标志物减弱了 hsCRP 和 MI 之间的关联，表明与全身炎症过程存在潜在联系。我们确定了三种代谢物生物标志物，它们的结合提高了弗雷明汉风险评分的预测价值。这三种代谢物对 hsCRP-MI 关联的减弱表明与全身炎症的潜在联系。
The comprehensive assaying of low-molecular-weight compounds, for example, metabolomics, provides a unique tool to uncover novel biomarkers and understand pathways underlying myocardial infarction (MI). We used a targeted metabolomics approach to identify biomarkers for MI and evaluate their involvement in the pathogenesis of MI. Using three independent, prospective cohorts (KORA S4, KORA S2 and AGES-REFINE), totalling 2257 participants without a history of MI at baseline, we identified metabolites associated with incident MI (266 cases). We also investigated the association between the metabolites and high-sensitivity C reactive protein (hsCRP) to understand the relation between these metabolites and systemic inflammation. Out of 140 metabolites, 16 were nominally associated (p<0.05) with incident MI in KORA S4. Three metabolites, arginine and two lysophosphatidylcholines (LPC 17:0 and LPC 18:2), were selected as biomarkers via a backward stepwise selection procedure in the KORA S4 and were significant (p<0.0003) in a meta-analysis comprising all three studies including KORA S2 and AGES-REFINE. Furthermore, these three metabolites increased the predictive value of the Framingham risk score, increasing the area under the receiver operating characteristic score in KORA S4 (from 0.70 to 0.78, p=0.001) and AGES-REFINE study (from 0.70 to 0.76, p=0.02), but was not observed in KORA S2. The metabolite biomarkers attenuated the association between hsCRP and MI, indicating a potential link to systemic inflammatory processes. We identified three metabolite biomarkers, which in combination increase the predictive value of the Framingham risk score. The attenuation of the hsCRP–MI association by these three metabolites indicates a potential link to systemic inflammation.
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大规模代谢组分析确定了出现冠心病的新生物标志物。
影响因子：
4.5
作者：
Ganna A;Salihovic S;Sundström J;Broeckling CD;Hedman AK;Magnusson PK;Pedersen NL;Larsson A;Siegbahn A;Zilmer M;Prenni J;Arnlöv J;Lind L;Fall T;Ingelsson E
通讯作者：
Ingelsson E
影响因子：
24
作者：
Ajani, Umed A.;Ford, Earl S.
通讯作者：
Ford, Earl S.
影响因子：
37.8
作者：
Cheng S;Rhee EP;Larson MG;Lewis GD;McCabe EL;Shen D;Palma MJ;Roberts LD;Dejam A;Souza AL;Deik AA;Magnusson M;Fox CS;O'Donnell CJ;Vasan RS;Melander O;Clish CB;Gerszten RE;Wang TJ
通讯作者：
Wang TJ
影响因子：
5
作者：
Ganna, Andrea;Reilly, Marie;Ingelsson, Erik
通讯作者：
Ingelsson, Erik
影响因子：
4.6
作者：
Mungrue, Imran N;Husain, Mansoor;Stewart, Duncan J
通讯作者：
Stewart, Duncan J