Tuesday, April 24, 2007

Contemporary Biomarkers

N Engl J Med 2007; 356:1472-1475, Apr 5, 2007

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

Thomas J. Wang, M.D., Philimon Gona, Ph.D., Martin G. Larson, Sc.D., Geoffrey H. Tofler, M.D., Daniel Levy, M.D., Christopher Newton-Cheh, M.D., M.P.H., Paul F. Jacques, D.Sc., Nader Rifai, Ph.D., Jacob Selhub, Ph.D., Sander J. Robins, M.D., Emelia J. Benjamin, M.D., Sc.M., Ralph B. D'Agostino, Ph.D., and Ramachandran S. Vasan, M.D.


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) p="0.02)." color="#000099">
Source Information From the Framingham Heart Study, Framingham, MA (T.J.W., P.G., M.G.L., D.L., C.N.-C., S.J.R., E.J.B., R.B.D., R.S.V.); the Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School (T.J.W., C.N.-C.), and the Department of Mathematics and Statistics, Boston University (P.G., M.G.L., R.B.D.) — both in Boston; the Royal North Shore Hospital, Sydney (G.H.T.); the National Heart, Lung, and Blood Institute, Bethesda, MD (D.L.); and the Jean Mayer Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (P.F.J., J.S.), the Department of Laboratory Medicine, Children's Hospital, Harvard Medical School (N.R.), and the Preventive Medicine and Cardiology Sections (D.L., E.J.B., R.S.V.) and the Division of Endocrinology, Nutrition, and Diabetes (S.J.R.), Boston Medical Center, Boston University School of Medicine — all in

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