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DURHAM, N.C. – Researchers at Duke University Medical Center
have discovered that otherwise healthy people who are prone to
anger, hostility and mild to moderate depressive symptoms
produce higher levels of a substance that promotes
cardiovascular disease and stroke.

The substance, C-reactive protein (CRP), has garnered
considerable attention for its role in both promoting and
predicting cardiovascular disease and stroke in initially
healthy people. It is produced by the liver in response to
inflammation, and inflammation has recently been shown to
underlie the plaque that forms inside arteries as they
clog.

The Duke study is the first to link this combination of
negative psychological attributes with higher levels of CRP in
people without traditional risk factors for heart disease, said
Edward Suarez, Ph.D., associate professor in the Duke
Department of Psychiatry and Behavioral Sciences.

Results of his study are published in the September, 2004,
issue of the journal Psychosomatic Medicine. The study was
funded by a grant from the National Heart, Lung and Blood
Institute.

People with traditional risk factors for heart disease –
obesity, smoking, diabetes, hypertension, high cholesterol and
sedentary lifestyles – have elevated CRP levels, said Suarez.
But a large number of individuals without these traditional
risk factors have elevated levels of CRP as well, without an
identifiable cause.

The Duke study demonstrates that anger, hostile behavior and
depressive symptoms could account for why apparently healthy
individuals have higher CRP levels and are thus at increased
risk for cardiovascular disease and stroke. Suarez said his
findings could also explain why people with mild to moderate
symptoms of depression are at increased risk for cardiac events
and early death – a link that has been clearly established but
without an underlying mechanism to explain why.

"Fifty percent of all heart attacks occur among people
without any traditional risk factors, so it is critical to
identify other factors that may underlie heart disease and the
inflammation that contributes to it," said Suarez.

In earlier studies, Suarez has shown that people who are
prone to anger, hostility and depressive symptoms respond to
stress with increased production of the stress hormone
norepinephrine. Scientific evidence suggests that an increase
in this stress hormone activates the inflammatory arm of the
immune system and triggers the expression of genes that cause
chronic, low-grade inflammation. This inflammation is
characterized by high levels of CRP, he said.

"Individuals with these psychological attributes may
evaluate their environment in a cynically hostile manner, and
thus respond with greater anger, which is often accompanied by
mild to moderate symptoms of depression," said Suarez. "These
psychological attributes tend to cluster within the same
individual, and the clustering of attributes may produce even
greater risk than any single trait alone."

Suarez said the levels of depressive symptoms and
angry/hostile moods necessary to raise CRP do not constitute
psychiatric conditions. "That is, you don't have to be
clinically depressed or have extreme and frequent bouts of
anger to show higher levels of CRP," he said.

In the Duke study, 121 healthy men and women were asked to
complete standard personality questionnaires in which they
described their psychological attributes, including anger,
hostility and depression. The volunteers did not have any
pre-existing conditions -- such as smoking, high blood
pressure, diabetes or heart disease -- that would predispose
them to having high CRP levels. High-sensitivity blood tests
were then conducted to measure CRP levels.

Respondents who were prone to anger, had high hostility
levels, and showed mild to moderate symptoms of depression had
two to three times higher CRP levels than their calmer
counterparts. The more pronounced their negative moods, the
higher CRP levels they had, the study showed.

The highest levels of CRP were in the range of 1.7 mg/L to
3.0 mg/L. While these levels are still considered relatively
low – fever, an active infection, or physical trauma is
associated with CRP levels above 10.0/mg/L –CRP levels in this
range are associated with a moderate to high risk of heart
attacks and strokes, said Suarez.

"CRP levels at this range are associated with inflammation
that is likely to eventually increase the risk of a heart
attack or stroke," he said. "If you add these psychological
attributes together with the known impact of traditional risk
factors, it could further elevate CRP levels."

Suarez has previously shown that hostile people who exhibit
symptoms of depression have higher levels of stress hormones
and circulating levels of an inflammatory substance called
interleukin 6, another marker of inflammation that has been
shown to predict heart disease in initially healthy people. The
current data build upon his earlier research and demonstrate
yet another mechanism through which the brain and the body
interact to contribute to poor health, he said.

"Most individuals tend to think of heart disease as a
condition that is associated with factors such as high
cholesterol, high blood pressure, smoking and sedentary
lifestyle," said Suarez. "Our findings, however, suggest the
development of heart disease may also be due to psychological
attributes that activate the inflammatory process shown to
predict and contribute to the development of heart
disease."