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Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics

Nature Medicine volume 8, pages 1439–1445 (2002)Cite this article

A Corrigendum to this article was published on 01 April 2003

Abstract

Although a wide range of risk factors for coronary heart disease have been identified from population studies, these measures, singly or in combination, are insufficiently powerful to provide a reliable, noninvasive diagnosis of the presence of coronary heart disease. Here we show that pattern-recognition techniques applied to proton nuclear magnetic resonance (1H-NMR) spectra of human serum can correctly diagnose not only the presence, but also the severity, of coronary heart disease. Application of supervised partial least squares-discriminant analysis to orthogonal signal-corrected data sets allows >90% of subjects with stenosis of all three major coronary vessels to be distinguished from subjects with angiographically normal coronary arteries, with a specificity of >90%. Our studies show for the first time a technique capable of providing an accurate, noninvasive and rapid diagnosis of coronary heart disease that can be used clinically, either in population screening or to allow effective targeting of treatments such as statins.

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Figure 1: Comparison of patients with severe atherosclerosis (TVD) and patients with normal coronary arteries (NCA).
Figure 2: Prediction of coronary artery status using the PLS-DA model.
Figure 3: Comparison of patients with different severity of coronary atherosclerosis.

References

  1. National Statistics Series DH1 no. 31, Mortality Statistics (1998). The Stationery Office (UK Government), London, England.

  2. Kjelsberg, M.O., Cutler, J.A. & Dolecek, T.A. Brief description of the Multiple Risk Factor Intervention Trial. Am. J. Clin. Nutr. 65 (Suppl. 1), 191S–195S (1997).

    Article  CAS  Google Scholar 

  3. Kuller, L.H. et al. Cigarette smoking and mortality. MRFIT Research Group. Prev. Med. 20, 638–654 (1991).

    Article  CAS  Google Scholar 

  4. Multiple Risk Factor Intervention Trial Research Group. Relationship between baseline risk factors and coronary heart disease and total mortality in the Multiple Risk Factor Intervention Trial. Prev. Med. 15, 254–273 (1986).

  5. McIlvain, H.E., McKinney, M.E., Thompson, A.V. & Todd, G.L. Application of the MRFIT smoking cessation program to a healthy, mixed-sex sample. Am. J. Prev. Med. 8, 165–170 (1992).

    Article  CAS  Google Scholar 

  6. Ross, R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340, 115–126 (1999).

    Article  CAS  Google Scholar 

  7. Cullen, P., Funke, H., Schulte, H. & Assmann, G. Lipoproteins and cardiovascular risk—from genetics to CHD prevention. Eur. Heart J. 19 (Suppl. C), C5–C11 (1998).

    PubMed  Google Scholar 

  8. Isles, C.G. & Paterson, J.R. Identifying patients at risk for coronary heart disease: Implications from trials of lipid-lowering drug therapy. Q.J. Med. 93, 567–574 (2000).

    Article  CAS  Google Scholar 

  9. Nicholson, J.K., Lindon, J.C. & Holmes, E. 'Metabonomics': Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181–1189 (1999).

    Article  CAS  Google Scholar 

  10. Nicholson, J.K. & Wilson, I.D. High resolution proton magnetic resonance spectroscopy of biological fluids Prog. Nucl. Magn. Reson. Spectrosc. 21, 449–501 (1989).

    Article  CAS  Google Scholar 

  11. Lindon, J.C., Holmes, E. & Nicholson, J.K. Pattern recognition methods and applications in biomedical magnetic resonance. Prog. Nucl. Magn. Reson. Spectrosc. 39, 1–40 (2001).

    Article  CAS  Google Scholar 

  12. Lindon, J.C., Nicholson, J.K.N., Holmes, E. & Everett, J.R. Metabonomics: metabolic processes studied by NMR spectroscopy of biofluids. Concepts Magn. Reson. 12, 289–320 (2000).

    Article  CAS  Google Scholar 

  13. Holmes, E. et al. Chemometric models for toxicity classification based on NMR spectra of biofluids. Chem. Res. Toxicol. 13, 471–478 (1999).

    Article  Google Scholar 

  14. Storck, T., von Brevern, M.C., Behrens, C.K., Scheel, J. & Bach, A. Transcriptomics in predictive toxicology. Curr. Opin. Drug Discov. Devel. 5, 90–97 (2002).

    CAS  PubMed  Google Scholar 

  15. Nicholson, J.K., Foxall, P.J., Spraul, M., Farrant, D.R. & Lindon, J.C. 750 MHz 1H and 1H-13C NMR spectroscopy of human blood plasma. Anal. Chem. 67, 793–811 (1995).

    Article  CAS  Google Scholar 

  16. Ala-Korpela, M. 1H-NMR spectroscopy of human blood plasma. Prog. Nucl. Magn. Reson. Spectrosc. 27, 475–554 (1995).

    Article  CAS  Google Scholar 

  17. Eriksson, L., Johansson, E., Kettanah-Wold, N. & Wold, S. Introduction to Multi and Megavariate Data Analysis Using Projection Methods (PCA and PLS-DA) (Umetrics AB, Malmo, Sweden, 1999).

    Google Scholar 

  18. Wold, S., Antti, H., Lindgren, F. & Ohman, J. Orthogonal signal correction of near-infrared spectra. Chemometrics Intelligent Lab. Systems 44, 175–185 (1998).

    Article  CAS  Google Scholar 

  19. Ala-Korpela, M., Hiltunen, Y. & Bell, J.D. Quantification of biomedical NMR data using artificial neural network analysis: Lipoprotein lipid profiles from 1H NMR data of human plasma. NMR Biomed. 8, 235–244 (1995).

    Article  CAS  Google Scholar 

  20. Otvos, J. In Handbook of Lipoprotein Testing (eds. Rifai, N., Warnick, R. & Dominiczak, M.) 497–508 (AACC Press, Washington DC, 1997).

    Google Scholar 

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Authors and Affiliations

  1. Biomedical Sciences Division, Biological Chemistry, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London, UK

    Joanne T. Brindle, Henrik Antti, Elaine Holmes, George Tranter & Jeremy K. Nicholson

  2. Department of Cardiology, Papworth Hospital NHS Trust, Cambridge, UK

    Hugh W.L. Bethell, Sarah Clarke & Peter M. Schofield

  3. GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, UK

    Elaine McKilligin

  4. Department of Medicine, Box 157, Addenbrooke's Hospital, Cambridge, UK

    David E. Mosedale & David J. Grainger

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  1. Joanne T. Brindle
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Correspondence to David J. Grainger.

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Competing interests

E.H., J.K.N and D.J.G. declare financial interest in this publication. These authors are named inventors on one or more patents filed partly as a result of the work described in this report, and these patents are assigned to Metabometrix Limited, a company in which E.H. and J.K.N. hold more than 5% equity stakes.

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Brindle, J., Antti, H., Holmes, E. et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat Med 8, 1439–1445 (2002). https://doi.org/10.1038/nm1202-802

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