Beijing, China - A multiple biomarker index, one that includes markers of inflammation, is only

modestly associated with increased risks of coronary heart disease and cardiovascular disease in
asymptomatic patients, according to the results of a new study [1]. The increased risk of events
for patients with a biomarker score above the median occurs mainly in those with a mild amount
of existing atherosclerosis, according to investigators.

Dr
Nathan
Wong

"Our purpose was to use both subclinical disease screening and the biomarker index to see if this
combined approach helped improve risk stratification in asymptomatic patients," lead
investigator Dr Nathan Wong (University of California, Irvine) told heartwire. "I don't think it's
entirely obvious, but the biomarkers might add to risk prediction in certain patients. We have a
limited sample with a limited number of events showing that maybe the biomarkers work in
people with intermediate levels of atherosclerosis. I do think, however, the results need further
validation."

Presenting the results of the study here at the World Congress of Cardiology, Wong said there
is a lot of interest in the potential role of new biomarkers and the concept of a multibiomarker
approach, where clinicians would be able to calculate risk scores based on various different
pathologies. Research in the past few years, however, has provided mixed results with regard to
the clinical utility of most biomarkers for the improvement of risk assessment.

One analysis of the Framingham Heart Study failed to show an improvement in the prediction
of cardiovascular events when adding 10 common contemporary biomarkers to standard risk
factors. An analysis of elderly men with and without cardiovascular disease in the Uppsala
Longitudinal Study of Adult Men (ULSAM), however, showed that the addition of several
biomarkers of cardiovascular and renal dysfunction significantly improved risk stratification for
death from cardiovascular causes. Both of these recent studies were reported by heartwire.

Biomarkers with nonredundant pathobiology

In this newest study, Wong said that his group was interested in possibly identifying certain
subgroups where the addition of biomarkers might result in an improvement in risk prediction.

"The concept here was to see if we could use different biomarkers that have nonredundant
pathobiology and perhaps combine these with subclinical disease testing with coronary calcium
as a way of assessing atherosclerotic burden," he said. "The way this might work would be in an
intermediate-risk population, where a patient might have a nominal LDL cholesterol cut point of
100 or 130 [mg/dL]. If you found patients with elevated biomarkers and an increased coronary
artery calcium score, we might bump that person to a higher-risk stratum, thereby treating them
more aggressively."

The group studied 1302 asymptomatic patients, mean age 59 years old, who received coronary
artery calcium (CAC) scanning as part of the Early Identification of Subclinical
Atherosclerosis by Noninvasive Imaging Research (EISNER) study. Calcium scores were
classified as none/minimal (CAC 0-9), mild (10-99), and moderate/significant (>100). The
biomarker index, consisting of high-sensitivity C-reactive protein (CRP), interleukin-6 (IL-6),
brain natriuretic peptide (BNP), myeloperoxidase (MPO), plasminogen activator inhibitor-1
(PAI-1), and angiotensinogen, was calculated by assigning points to each biomarker depending
on its measurement, with zero points if the measure were in the first quartile or three points if it
were in the highest quartile.

After an average follow-up of four years, regardless of the biomarker index, coronary heart
disease and cardiovascular disease event rates were similar in patients with low CAC scores and
in those with high CAC scores. Among those with intermediate CAC scores—those considered
to have mild atherosclerosis disease burden—coronary heart disease and cardiovascular disease
event rates differed significantly among those who fell above or below the median biomarker
index score.