Multiple biomarkers for the prediction of first major cardiovascular events and death.
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.
Wang
Thomas J
TJ
Framingham Heart Study, Framingham, MA, USA. tjwang@partners.org
Gona
Philimon
P
Larson
Martin G
MG
Tofler
Geoffrey H
GH
Levy
Daniel
D
Newton-Cheh
Christopher
C
Jacques
Paul F
PF
Rifai
Nader
N
Selhub
Jacob
J
Robins
Sander J
SJ
Benjamin
Emelia J
EJ
D'Agostino
Ralph B
RB
Vasan
Ramachandran S
RS
D015415:Biomarkers / Q000097:blood* / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009026:Mortality; D015999:Multivariate Analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors
D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D002097:C-Reactive Protein