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Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death

Open access
Wang, Thomas J., Gona, Philimon, Larson, Martin G., Tofler, Geoffrey H., Levy, Daniel, Newton-Cheh, Christopher, Jacques, Paul F., Rifai, Nader, Selhub, Jacob, Robins, Sander J., Benjamin, Emelia J., D'Agostino, Ralph B., Vasan, Ramachandran S.·2006·New England Journal of Medicine

Abstract

BACKGROUND: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. METHODS: We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, and homocysteine; and the urinary albumin-to-creatinine ratio. RESULTS: During follow-up (median, 7.4 years), 207 participants died and 169 had a first major cardiovascular event. In Cox proportional-hazards models adjusting for conventional risk factors, the following biomarkers most strongly predicted the risk of death (each biomarker is followed by the adjusted hazard ratio per 1 SD increment in the log values): B-type natriuretic peptide level (1.40), C-reactive protein level (1.39), the urinary albumin-to-creatinine ratio (1.22), homocysteine level (1.20), and renin level (1.17). The biomarkers that most strongly predicted major cardiovascular events were B-type natriuretic peptide level (adjusted hazard ratio, 1.25 per 1 SD increment in the log values) and the urinary albumin-to-creatinine ratio (1.20). Persons with "multimarker" scores (based on regression coefficients of significant biomarkers) in the highest quintile as compared with those with scores in the lowest two quintiles had elevated risks of death (adjusted hazard ratio, 4.08; P<0.001) and major cardiovascular events (adjusted hazard ratio, 1.84; P=0.02). However, the addition of multimarker scores to conventional risk factors resulted in only small increases in the ability to classify risk, as measured by the C statistic. CONCLUSIONS: For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.

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Metadata

Authors
Wang, T. J., Gona, P., Larson, M. G., Tofler, G. H., Levy, D., Newton-Cheh, C., Jacques, P. F., Rifai, N., Selhub, J., Robins, S. J., Benjamin, E. J., D'Agostino, R. B., & Vasan, R. S.
Venue
New England Journal of Medicine
Published
2006-12-21
Volume
355
Issue
25
Pages
2631-2639
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
OpenAlex
W2133685977
Cited by
1,343
References
8
FWCI
112.83
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death. https://app.cochat.ai/papers/10.1056/nejmoa055373
The paper
Wang, T. J., Gona, P., Larson, M. G., Tofler, G. H., Levy, D., Newton-Cheh, C., Jacques, P. F., Rifai, N., Selhub, J., Robins, S. J., Benjamin, E. J., D'Agostino, R. B., & Vasan, R. S. (2006). Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death. New England Journal of Medicine. https://doi.org/10.1056/nejmoa055373

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