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

A.A.M. Vaarhorst, A. Verhoeven, C.M. Weller, S. Böhringer, S. Göraler, A. Meissner, A.M. Deelder, P. Henneman, A.P.M. Gorgels, P.A. van den Brandt, L.J. Schouten, M.M. van Greevenbroek, A.H.H. Merry, W.M.M. Verschuren, A.M.J.M. van den Maagdenberg, K.W. van Dijk, A. Isaacs, D. Boomsma, B.A. Oostra, C.M. van DuijnJ.W. Jukema, J.M.A. Boer, E. Feskens, B.T. Heijmans, P.E. Slagboom

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Background 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. Methods and results 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). Conclusion 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.
Original languageEnglish
Pages (from-to)45-52.e7
JournalAmerican Heart Journal
Volume168
Issue number1
DOIs
Publication statusPublished - 1 Jan 2014

Cite this

Vaarhorst, A. A. M., Verhoeven, A., Weller, C. M., Böhringer, S., Göraler, S., Meissner, A., ... Slagboom, P. E. (2014). A metabolomic profile is associated with the risk of incident coronary heart disease. American Heart Journal, 168(1), 45-52.e7. https://doi.org/10.1016/j.ahj.2014.01.019
Vaarhorst, A.A.M. ; Verhoeven, A. ; Weller, C.M. ; Böhringer, S. ; Göraler, S. ; Meissner, A. ; Deelder, A.M. ; Henneman, P. ; Gorgels, A.P.M. ; van den Brandt, P.A. ; Schouten, L.J. ; van Greevenbroek, M.M. ; Merry, A.H.H. ; Verschuren, W.M.M. ; van den Maagdenberg, A.M.J.M. ; van Dijk, K.W. ; Isaacs, A. ; Boomsma, D. ; Oostra, B.A. ; van Duijn, C.M. ; Jukema, J.W. ; Boer, J.M.A. ; Feskens, E. ; Heijmans, B.T. ; Slagboom, P.E. / A metabolomic profile is associated with the risk of incident coronary heart disease. In: American Heart Journal. 2014 ; Vol. 168, No. 1. pp. 45-52.e7.
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abstract = "Background 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. Methods and results 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). Conclusion 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.",
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Vaarhorst, AAM, Verhoeven, A, Weller, CM, Böhringer, S, Göraler, S, Meissner, A, Deelder, AM, Henneman, P, Gorgels, APM, van den Brandt, PA, Schouten, LJ, van Greevenbroek, MM, Merry, AHH, Verschuren, WMM, van den Maagdenberg, AMJM, van Dijk, KW, Isaacs, A, Boomsma, D, Oostra, BA, van Duijn, CM, Jukema, JW, Boer, JMA, Feskens, E, Heijmans, BT & Slagboom, PE 2014, 'A metabolomic profile is associated with the risk of incident coronary heart disease', American Heart Journal, vol. 168, no. 1, pp. 45-52.e7. https://doi.org/10.1016/j.ahj.2014.01.019

A metabolomic profile is associated with the risk of incident coronary heart disease. / Vaarhorst, A.A.M.; Verhoeven, A.; Weller, C.M.; Böhringer, S.; Göraler, S.; Meissner, A.; Deelder, A.M.; Henneman, P.; Gorgels, A.P.M.; van den Brandt, P.A.; Schouten, L.J.; van Greevenbroek, M.M.; Merry, A.H.H.; Verschuren, W.M.M.; van den Maagdenberg, A.M.J.M.; van Dijk, K.W.; Isaacs, A.; Boomsma, D.; Oostra, B.A.; van Duijn, C.M.; Jukema, J.W.; Boer, J.M.A.; Feskens, E.; Heijmans, B.T.; Slagboom, P.E.

In: American Heart Journal, Vol. 168, No. 1, 01.01.2014, p. 45-52.e7.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A metabolomic profile is associated with the risk of incident coronary heart disease

AU - Vaarhorst, A.A.M.

AU - Verhoeven, A.

AU - Weller, C.M.

AU - Böhringer, S.

AU - Göraler, S.

AU - Meissner, A.

AU - Deelder, A.M.

AU - Henneman, P.

AU - Gorgels, A.P.M.

AU - van den Brandt, P.A.

AU - Schouten, L.J.

AU - van Greevenbroek, M.M.

AU - Merry, A.H.H.

AU - Verschuren, W.M.M.

AU - van den Maagdenberg, A.M.J.M.

AU - van Dijk, K.W.

AU - Isaacs, A.

AU - Boomsma, D.

AU - Oostra, B.A.

AU - van Duijn, C.M.

AU - Jukema, J.W.

AU - Boer, J.M.A.

AU - Feskens, E.

AU - Heijmans, B.T.

AU - Slagboom, P.E.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background 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. Methods and results 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). Conclusion 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.

AB - Background 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. Methods and results 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). Conclusion 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.

U2 - 10.1016/j.ahj.2014.01.019

DO - 10.1016/j.ahj.2014.01.019

M3 - Article

VL - 168

SP - 45-52.e7

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

IS - 1

ER -

Vaarhorst AAM, Verhoeven A, Weller CM, Böhringer S, Göraler S, Meissner A et al. A metabolomic profile is associated with the risk of incident coronary heart disease. American Heart Journal. 2014 Jan 1;168(1):45-52.e7. https://doi.org/10.1016/j.ahj.2014.01.019