A metabolomic profile is associated with the risk of incident coronary heart disease

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• 作者：Anika A.M. Vaarhorst ; MSc^a ; ^s ; ^{a.a.m.vaarhorst@lumc.nl" class="auth_mail} ; Aswin Verhoeven ; PhD^b ; ^s ; Claudia M. Weller ; MD^c ; ^s ; Stefan Bö ; hringer ; MD ; PhD^d ; Sibel Gö ; raler ; MSc^b ; Axel Meissner ; PhD^b ; André ; M. Deelder ; PhD^b ; Peter Henneman ; PhD^c ; Anton P.M. Gorgels ; MD ; PhD^e ; Piet A. van den Brandt ; PhD^f ; ^g ; Leo J. Schouten ; MD ; PhD^g ; Marleen M. van Greevenbroek ; PhD^h ; Audrey H.H. Merry ; PhD^f ; W.M. Monique Verschuren ; PhDⁱ ; Arn M.J.M. van den Maagdenberg ; PhD^c ; ^j ; Ko Willems van Dijk ; PhD^c ; ^k ; Aaron Isaacs ; PhD^l ; Dorret Boomsma ; PhD^m ; Ben A. Oostra ; PhD^l ; Cornelia M. van Duijn ; PhD^l ; J. Wouter Jukema ; MD ; PhDⁿ ; ^o ; ^p ; Jolanda M.A. Boer ; PhDⁱ ; Edith Feskens ; PhD^q ; Bastiaan T. Heijmans ; PhD^a ; P. Eline Slagboom ; PhD^a ; ^r ; ^{P.Slagboom@lumc.nl" class="auth_mail}
• 刊名：American Heart Journal
• 出版年：July 2014
• 年：2014
• 卷：168
• 期：1
• 页码：45-52.e7
• 全文大小：554 K

文摘

Metabolomics, defined as the comprehensive identification and quantification of low-molecular-weight metabolites to be found in a biological sample, has been put forward as a potential tool for classifying individuals according to their risk of coronary heart disease (CHD). Here, we investigated whether a single-point blood measurement of the metabolome is associated with and predictive for the risk of CHD.

id="absSec_2">Methods and results

id="sp0015">We obtained proton nuclear magnetic resonance spectra in 79 cases who developed CHD during follow-up (median 8.1 years) and in 565 randomly selected individuals. In these spectra, 100 signals representing 36 metabolites were identified. Applying least absolute shrinkage and selection operator regression, we defined a weighted metabolite score consisting of 13 proton nuclear magnetic resonance signals that optimally predicted CHD. This metabolite score, including signals representing a lipid fraction, glucose, valine, ornithine, glutamate, creatinine, glycoproteins, citrate, and 1.5-anhydrosorbitol, was associated with the incidence of CHD independent of traditional risk factors (TRFs) (hazard ratio 1.50, 95% CI 1.12-2.01). Predictive performance of this metabolite score on its own was moderate (C-index 0.75, 95% CI 0.70-0.80), but after adding age and sex, the C-index was only modestly lower than that of TRFs (C-index 0.81, 95% CI 0.77-0.85 and C-index 0.82, 95% CI 0.78-0.87, respectively). The metabolite score was also associated with prevalent CHD independent of TRFs (odds ratio 1.59, 95% CI 1.19-2.13).

id="absSec_3">Conclusion

id="sp0020">A metabolite score derived from a single-point metabolome measurement is associated with CHD, and metabolomics may be a promising tool for refining and improving the prediction of CHD.