Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts.
Serum metabolites and risk of myocardial infarction and ischemic stroke: a targeted metabolomic approach in two German prospective cohorts.
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DOI：
10.1007/s10654-017-0333-0
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发表时间：
2018-01
影响因子：
13.6
通讯作者：
Pischon T
中科院分区：
文献类型：
--
作者：
Floegel A;Kühn T;Sookthai D;Johnson T;Prehn C;Rolle-Kampczyk U;Otto W;Weikert C;Illig T;von Bergen M;Adamski J;Boeing H;Kaaks R;Pischon T
前瞻性队列中的代谢组学方法可以为健康人群中与心血管疾病（CVD）风险较高相关的早期代谢紊乱提供独特的快照。我们在欧洲癌症与营养前瞻性研究（EPIC）-波茨坦（27，548名成人）和海德堡（25，540名成人）队列中研究了105种血清代谢物（包括酰基肉毒碱、氨基酸、磷脂和己糖）与心肌梗死（MI）和缺血性卒中风险的相关性。使用病例队列设计，我们测量了抽血时无CVD和糖尿病但在随访期间（平均7.8年和7.3年）发生MI（n = 204和n = 228）或卒中（n = 147和n = 121）的个体以及随机抽取的子队列（n = 2214和n = 770）中的代谢物。我们使用了考克斯回归分析，并使用荟萃分析合并结果。独立于经典CVD风险因素，两个队列中有10种代谢物与MI风险相关，包括鞘磷脂、二酰基磷脂酰胆碱和酰基烷基磷脂酰胆碱，代谢物浓度每增加一个标准差，合并相对风险在1.21-1.40范围内。代谢产物与总胆固醇和LDL胆固醇呈正相关（r范围为0.13 - 0.57）。当另外调整总胆固醇、LDL胆固醇和HDL胆固醇、甘油三酯和C反应蛋白时，酰基烷基磷脂酰胆碱C36：3和二酰基磷脂酰胆碱C38：3和C40：4仍然与MI风险相关。当添加到经典CVD风险模型中时，这些代谢物进一步改善了CVD预测（EPIC-Potsdam中的c-统计量从0.8365增加到0.8384，EPIC-Heidelberg中从0.8344增加到0.8378）。没有一种代谢物与中风风险一致相关。鞘磷脂和磷脂酰胆碱代谢的改变，特别是花生四烯酸途径的代谢物与健康成人的MI风险独立相关。本文的在线版本（10.1007/s10654-017-0333-0）包含补充材料，可供授权用户使用。
Metabolomic approaches in prospective cohorts may offer a unique snapshot into early metabolic perturbations that are associated with a higher risk of cardiovascular diseases (CVD) in healthy people. We investigated the association of 105 serum metabolites, including acylcarnitines, amino acids, phospholipids and hexose, with risk of myocardial infarction (MI) and ischemic stroke in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) and Heidelberg (25,540 adults) cohorts. Using case-cohort designs, we measured metabolites among individuals who were free of CVD and diabetes at blood draw but developed MI (n = 204 and n = 228) or stroke (n = 147 and n = 121) during follow-up (mean, 7.8 and 7.3 years) and among randomly drawn subcohorts (n = 2214 and n = 770). We used Cox regression analysis and combined results using meta-analysis. Independent of classical CVD risk factors, ten metabolites were associated with risk of MI in both cohorts, including sphingomyelins, diacyl-phosphatidylcholines and acyl-alkyl-phosphatidylcholines with pooled relative risks in the range of 1.21–1.40 per one standard deviation increase in metabolite concentrations. The metabolites showed positive correlations with total- and LDL-cholesterol (r ranged from 0.13 to 0.57). When additionally adjusting for total-, LDL- and HDL-cholesterol, triglycerides and C-reactive protein, acyl-alkyl-phosphatidylcholine C36:3 and diacyl-phosphatidylcholines C38:3 and C40:4 remained associated with risk of MI. When added to classical CVD risk models these metabolites further improved CVD prediction (c-statistics increased from 0.8365 to 0.8384 in EPIC-Potsdam and from 0.8344 to 0.8378 in EPIC-Heidelberg). None of the metabolites was consistently associated with stroke risk. Alterations in sphingomyelin and phosphatidylcholine metabolism, and particularly metabolites of the arachidonic acid pathway are independently associated with risk of MI in healthy adults. The online version of this article (10.1007/s10654-017-0333-0) contains supplementary material, which is available to authorized users.
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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：
7.7
作者：
Floegel A;Stefan N;Yu Z;Mühlenbruch K;Drogan D;Joost HG;Fritsche A;Häring HU;Hrabě de Angelis M;Peters A;Roden M;Prehn C;Wang-Sattler R;Illig T;Schulze MB;Adamski J;Boeing H;Pischon T
通讯作者：
Pischon T
影响因子：
8.2
作者：
Langenberg, C.;Sharp, S.;Forouhi, N. G.;Franks, P. W.;Schulze, M. B.;Kerrison, N.;Ekelund, U.;Barroso, I.;Panico, S.;Tormo, M. J.;Spranger, J.;Griffin, S.;van der Schouw, Y. T.;Amiano, P.;Ardanaz, E.;Arriola, L.;Balkau, B.;Barricarte, A.;Beulens, J. W. J.;Boeing, H.;Bueno-de-Mesquita, H. B.;Buijsse, B.;Chirlaque Lopez, M. D.;Clavel-Chapelon, F.;Crowe, F. L.;de Lauzon-Guillan, B.;Deloukas, P.;Dorronsoro, M.;Drogan, D.;Froguel, P.;Gonzalez, C.;Grioni, S.;Groop, L.;Groves, C.;Hainaut, P.;Halkjaer, J.;Hallmans, G.;Hansen, T.;Huerta Castano, J. M.;Kaaks, R.;Key, T. J.;Khaw, K. T.;Koulman, A.;Mattiello, A.;Navarro, C.;Nilsson, P.;Norat, T.;Overvad, K.;Palla, L.;Palli, D.;Pedersen, O.;Peeters, P. H.;Quiros, J. R.;Ramachandran, A.;Rodriguez-Suarez, L.;Rolandsson, O.;Romaguera, D.;Romieu, I.;Sacerdote, C.;Sanchez, M. J.;Sandbaek, A.;Slimani, N.;Sluijs, I.;Spijkerman, A. M. W.;Teucher, B.;Tjonneland, A.;Tumino, R.;van der A, D. L.;Verschuren, W. M. M.;Tuomilehto, J.;Feskens, E.;McCarthy, M.;Riboli, E.;Wareham, N. J.
通讯作者：
Wareham, N. J.
DOI：
10.1161/01.atv.20.12.2614
发表时间：
2000-12-01
影响因子：
8.7
作者：
Jiang, XC;Paultre, F;Tall, AR
通讯作者：
Tall, AR
影响因子：
3.3
作者：
Koizumi, S.;Yamamoto, S.;Namba, H.
通讯作者：
Namba, H.