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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.

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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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  2. Henrik Antti
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  3. Elaine Holmes
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  4. George Tranter
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  5. Jeremy K. Nicholson
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  6. Hugh W.L. Bethell
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  9. Elaine McKilligin
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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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