|
Ability of biomarkers to predict risk
of heart disease, stroke appears limited
Study suggests new biomarkers will
be needed to assess individual risk levels
BOSTON - December 20, 2006 - A study of the use of biomarkers
to predict the risk of cardiovascular disease and death in an apparently
healthy population has found that, even though some measurements
are associated with future cardiovascular events, their usefulness
for predicting risk in individuals may be limited. The report from
the Framingham
Heart Study appears in the Dec. 21 New England Journal of
Medicine.
"We found that several contemporary biomarkers were associated
with future cardiovascular disease or death, over and above what
was indicated by established risk factors; but even in combination
their utility for risk prediction was modest," says Thomas
J. Wang, MD, of the Massachusetts General Hospital (MGH) Division
of Cardiology, the report's lead author. "High biomarker levels
can successfully identify groups of people at risk, but their ability
to predict an individual person's risk - a goal of 'personalized
medicine' - is still limited."
Many previous studies have identified potential biomarkers - laboratory
measurements that may indicate a particular biological state - of
cardiovascular risk. These include blood levels of C-reactive protein,
B-type natriuretic peptide (BNP), and homocysteine, elevated levels
of which have been associated with increased risk. However, few
studies have looked at the use of multiple biomarkers, either to
compare their usefulness or to evaluate the testing of several markers
at once.
The current study was designed specifically to look at the ability
of a multimarker testing approach to evaluate cardiovascular risk
in a group of apparently healthy individuals. Participants were
members of the Framingham Offspring Study, which follows a group
of adult children of participants in the original Framingham Heart
Study to evaluate risk factors for the development of cardiovascular
disease. During participants' regular study visits between 1995
and 1998, they were tested for 10 potential biomarkers of cardiovascular
risk, along with the usual history, physical examination and other
assessments taken as part of the overall Offspring Study. Those
known to have a prior heart attack or stroke were excluded from
the biomarker study.
Among the 3,200 participants in the biomarker study, 169 experienced
a major cardiovascular event - such as heart attack, stroke or cardiac
death - during the study period of up to 10 years. The biomarkers
that proved most useful in predicting future cardiovascular events
were BNP and urinary albumin content. BNP appeared to be a stronger
predictor of risk than C-reactive protein, possibly the best-known
cardiovascular biomarker. However, even though those with high multimarker
scores had twice the risk of a cardiovascular event as those with
low scores, the information provided by the biomarkers only slightly
improved predictions based on such conventional risk factors as
hypertension, cholesterol levels and smoking.
"There has been a great deal of enthusiasm among cardiologists
over the potential of biomarkers, but our findings suggest that
we need to identify additional biomarkers to be able to predict
individual risk in a useful fashion," says Wang. "Newer
biological approaches, such as genomics and proteomics, may give
us tools that can help identify these new biomarkers." Wang
is an assistant professor of Medicine at Harvard Medical School.
"This important study shows that conventional risk factors
have stood the test of time and are still good predictors of risk,
while at the same time adding to the growing body of information
on novel biomarkers," says Elizabeth G. Nabel, MD, director
of the National
Heart, Lung and Blood Institute (NHLBI), which sponsors the
Framingham Heart Study. "Although there was only a modest improvement
in risk assessment when new risk factors were added to conventional
ones, it was enough to show the potential value of the newer markers.
We look to further research to identify other biomarkers that are
more predictive of risk, which could also have implications for
the development of new treatments for cardiovascular disease."
The study's senior author is Ramachandran Vasan, MD, from the Boston
University School of Medicine. Co-authors of the NEJM report are
Christopher Newton-Cheh, MD, MPH, MGH Cardiology; Philimon Gona,
PhD, Martin Larson, ScD, and Ralph D'Agostino, PhD, Boston University;
Geoffrey Tofler, MD, Royal North Shore Hospital, Sydney, Australia;
Paul Jacques, DSc, and Jacob Selhub, PhD, Tufts University; Nader
Rifai, PhD, Children's Hospital Boston; and Daniel Levy, MD, Emelia
Benjamin MD, ScM, and Sander Robins, MD, Boston University School
of Medicine. Levy is also director of the Framingham Heart Study,
for which most of the co-authors are investigators, and is associated
with NHLBI. Additional support for the NEJM study came from grants
from the U.S. Department of Agriculture, the American Diabetes Association
and the American Heart Association.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, transplantation biology and photomedicine. MGH and Brigham
and Women's Hospital are founding members of Partners HealthCare
HealthCare System, a Boston-based integrated health care delivery
system.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
|
|
|
