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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #211435
Title: Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death

Author
item WANG, THOMAS - FRAMINGHAM HEART STUDY
item GONA, PHILIMON - FRAMINGHAM HEART STUDY
item LARSON, MARTIN - FRAMINGHAM HEART STUDY
item TOFFLER, GEOFFREY - ROYAL NO.SHORE HOSP. AUST
item LEVY, DANIEL - FRAMINGHAM HEART STUDY
item NEWTON-CHEH, CHRISTOPHER - FRAMINGHAM HEART STUDY
item Jacques, Paul
item RIFAI, NADER - HARVARD MEDICAL SCHOOL
item Selhub, Jacob
item ROBINS, SANDER - FRAMINGHAM HEART STUDY
item BENJAMIN, EMELIA - FRAMINGHAM HEART STUDY
item D'AGOSTIONO, RALPH - FRAMINGHAM HEART STUDY
item VASAN, RAMACHANDRAN - FRAMINGHAM HEART STUDY

Submitted to: New England Journal of Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/1/2006
Publication Date: 12/21/2006
Citation: Wang, T.J., Gona, P., Larson, M.G., Toffler, G.H., Levy, D., Newton-Cheh, C., Jacques, P., Rifai, N., Selhub, J., Robins, S.J., Benjamin, E.J., D'Agostiono, R.B., Vasan, R.S. 2006. Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death. New England Journal of Medicine. 355(25): 2631-9.

Interpretive Summary: There are people which are more prone to heart disease than others. These people would normally have hypertension, high cholesterol, diabetes and others. In general these are termed risk factors. Over the years other new risk factors have been identified. In this study we assessed the extent to which newly identified risk factors contribute to chance of heart disease or death from heart disease. Homocysteine is an amino acid which plays important role in the body, but becomes a risk factor when its level in the blood is elevated. In this study homocysteine as well as other newly identified risk factor for heart disease and mortality were assessed for there added contribution to the traditional risk factor. We found that the contribution of these risk factors is relatively small.

Technical Abstract: Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. 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. 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. For assessing risk in individual persons, the use of the 10 contemporary biomarkers that we studied adds only moderately to standard risk factors.