It has all the makings of a great detective novel: an
unsolved crime, plenty of evidence at the scene, a range
of known suspects and one inconspicuous player lurking
in the shadows. Atherosclerosis causes roughly half of
all adult deaths in first world countries. Factors that
increase risk, such as high cholesterol and smoking, are
well known, but the cause in 40% of cases remains unsolved.
In a search for new clues, recent research has pointed
a finger at Chlamydia pneumoniae as a potential
culprit in heart disease.
Reminiscent of the relationship
between peptic ulcer disease and Helicobacter pylori,
past research hints of a link between heart disease
and several infectious agents, including herpes simplex,
cytomegalovirus and coxsackie B virus. Other data support
the idea that atherosclerosis is a chronic inflammatory
disease, leading researchers on a hunt for a microbial
cause.
So how exactly does C pneumoniae
fit into the big picture of heart disease? Is this microbe
innocent or guilty as charged? Two recent studies give
us some clues, bringing us closer to solving this mystery.
In the first study published in the April 15 issue of
Clinical Infectious Diseases, lead author Christine
Arcari, PhD, of the University of Wisconsin, and colleagues,
found that high levels of C pneumoniae antibodies
in blood were associated with the occurrence of heart
attack.
The researchers analyzed blood
samples from 600 active-duty US military men aged 30-50.
The cases were equally divided between men who had been
hospitalized for a first heart attack and a group of
controls matched for age, race and time of specimen
collection. The association between high C pneumoniae
antibodies and heart attack occurrence was particularly
strong in blood collected one to five years before patients
had their first heart attacks. By contrast, evidence
of cytomegalovirus infection demonstrated no such association
with acute myocardial infarction (MI). But does this
prove there's a connection?
CONFLICTING
EVIDENCE
"We don't understand how Chlamydia fits into
the pathogenesis of [heart attacks]," admitted Dr Arcari
in an earlier statement. "We don't fully understand
why we're seeing this association on a biologic level."
Previous studies of C pneumoniae and acute MI
or coronary artery disease have had conflicting results
—some trials had demonstrable associations between
the bacterial infection and heart attacks, but not all
of them showed this trend.
The organism first came under suspicion
when Dr Pekka Saikku and colleagues published a study
in October 1988 in The Lancet. The researchers
showed that people with coronary artery disease were
more likely than healthy control subjects to have circulating
antibodies to C pneumoniae. They concluded in
their study that "chronic chlamydial infection could
be a factor in the pathogenesis of cardiovascular diseases."
ALL
IN THE FAMILY
Members of the Chlamydia family are responsible
for a variety of diseases like chlamydia and conjunctivitis.
Instead of causing venereal disease,
C pneumoniae leads to respiratory problems that
resemble the flu and can progress to pneumonia or bronchitis.
About 10% of pneumonia cases worldwide are linked to
C pneumoniae infection. And now it seems that
this microbe may also attack the heart.
However, Dr Arcari notes that we
don't yet know whether or not ridding the body of the
infection would have any beneficial effect on heart
health. Given the correlation between bacterial infection
with this strain and the incidence of heart disease,
the idea that a simple antibiotic could be the ultimate
cure for heart disease is a tantalizing one. But the
answer is not that simple.
ANTIBIOTICS
NOT THE ANSWER
A substantial, longterm study published in the April
21 issue of the New England Journal of Medicine (NEJM)
weighs in against antibiotic therapy as a way to prevent
the recurrence of cardiac-related events, including
heart attacks, angina and stroke.
"The study followed the fates of
4,012 patients who took the antibiotic gatifloxacin
or a placebo for up to two years after experiencing
a cardiac event. The average age of participants was
58, and 22% were women. The trial was sponsored by Bristol-Myers
Squibb and Sankyo — the makers of this medication.
The same proportion of participants
taking gatifloxacin died and/or experienced another
cardiac event (23.7%) as compared to those who took
the placebo (25.1%). Likewise, none of the other factors
measured in the trial, including antibody titers to
Chlamydia and C-reactive protein, differed between
the treatment and placebo groups.
Animal experiments have found that
antibiotic therapy prevents the buildup of artery-clogging
plaque, implying that Chlamydia triggers plaque formation.
Research suggests that the bacterium invokes a vascular
inflammatory response that may open the door for plaque
formation.
TOO
LITTLE, TOO LATE?
"Although Chlamydia pneumoniae may have
played a role in starting the process of atherosclerosis,
once patients have documented heart disease, it appears
to be too late to treat the infection," said study author
Dr Christopher Cannon from Harvard Medical School in
a press release from the Brigham and Women's Hospital.
"Instead, we need to focus on reducing
the cholesterol build-up and inflammation in the arteries,
using high-dose statins — as shown in this same
study — and other treatments."
In addition to monitoring cardiac
health, the researchers measured antibody levels to
Chlamydia throughout the trial. Treatment with
antibiotic did not affect Chlamydia antibody
levels, which suggests that the patients didn't have
an active infection at the time. If there's no active
infection then there's nothing for the antibiotic to
kill.
Another trial published in the
same issue showed the antibiotic azithromycin also failed
to protect patients with stable coronary artery disease
from a second cardiac event. So it may be time for researchers
to stop thinking of bacterial infections as the bugaboo
of cardiovascular disease. Until more pieces of this
puzzle fall into place, physicians would do well to
stick to proven treatments like statins, antiplatelet
therapy, beta-blockers and ACE inhibitors.
NEJM Apr 21, 2005;352(16):1646-54
Clin Infect Dis Apr 15, 2005;40(8):1123-30
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