Depression and heart disease: What's the link?
April 20, 2009
Mitchell Finkel, MD, a cardiologist at
the Clarksburg VA in West Virginia,
likes to point out that the word "heart"
appears more than 700 times in the Bible,
"mostly in the context of your emotions."
Indeed, people over the ages have
viewed the heart as the seat of the emotions.
The link is entrenched in our language:
Those who are grieving have a "broken
heart." The "heart sings" in those who are
happy. Is the connection merely figurative,
poetic? Or is there a biological basis for the
metaphor?
Researchers have found, in study after
study over decades, an undeniable link
between emotional illness—namely
depression—and heart disease. Not only is
depression common among those with heart
disease—in fact, it puts patients at greater
risk for dying—but it also appears to play a
role in causing heart disease in the first
place.
"There are some studies going back 50
years demonstrating that depression leads to
heart disease," notes Jeffrey Scherrer, PhD,
a psychiatry researcher at the St. Louis VA
and Washington University. He was lead
author on a recent study of more than 1,200
male twins who served in the military
during the Vietnam era. Men who reported
depression when they were surveyed in
1992 were twice as likely to develop heart
disease in the ensuing years. Even among
twins, who share similar or identical genetic
vulnerabilities to disease, only those who
experienced depression were at greater
cardiovascular risk.
But how exactly does depression
increase heart risk? One school of thought is
that depression is a marker for certain
behaviors that harm the body, including the
cardiovascular system. Smoking, physical
inactivity, poor diet and non-compliance
with medical treatment are known to bring
on or worsen many ailments, ranging from
heart disease to the common cold. But
there's also evidence suggesting that the
mental state of depression itself,
independent of any physically unhealthy
behaviors, triggers a cascade of hormonal
and other changes in the body that damage
the heart or blood vessels. Sorting out all
these variables and understanding how they
interact is a huge theme in medical research.
The inactivity factor
Mary Whooley, MD, an internist and
epidemiologist at the San Francisco VA,
believes behavior is key. Her team of
investigators on the "Heart and Soul Study"
followed more than 1,000 heart patients for
an average of nearly five years. The goal
was to tease out which physiological or
behavioral factors were most influential in
the pathway from depression to heart
disease. Their main finding, reported last
fall in the Journal of the American Medical
Association, was that "the association
between depressive symptoms and adverse
cardiovascular events was largely explained
by behavioral factors, particularly physical
inactivity."
Whooley: "Very often, patients with
depression don't exercise, which makes
them feel more depressed, which in turn
leads to their exercising even less. It's a
vicious cycle that leads directly to heart
disease."
Finkel, who conducts animal and clinical
research at VA and West Virginia University,
has a different view. He points to
experiments in which rats bred to be more
susceptible to emotional stress—he says
it's a close-enough model for
depression—are more likely to go into
heart failure when they are restrained.
"Here's an animal model that doesn't
have any behavioral issues but is
basically programmed differently," says
Finkel. He doesn't deny that depressionrelated
lifestyle factors such as smoking
or physical inactivity obviously
contribute to a higher risk for heart
disease. But he asserts that physiological
factors that are part of the depression
profile—though not necessarily linked to
any particular behavior—are just as
critical in the equation.
Cardiac abnormalities part
of depression
Researchers have identified several
biological changes that occur in people
with depression, any of which could
reasonably make them more susceptible
to heart attacks, stroke, heart failure or
other cardiovascular maladies: Their
hearts beat faster. They tend to have high
blood pressure. Their hearts don't adjust
well when they switch activities—from
walking to sitting, for example. They
have sticky platelets, which increases the
risk of harmful blood clots. They have
low levels of omega-3 fatty acids and
high levels of the stress hormone
cortisol.
Some of these factors may be
aggravated by smoking, say, or poor diet.
But Finkel and others believe there are
still baseline abnormalities in depressed
patients, independent of their unhealthy
behaviors. He points out that prenatally
stressed rats—his depression model—have some of the same biomarkers.
Figuring out how all the lifestyle and
biological factors interact is enough to make
a researcher's head spin. So why bother?
Isn't it enough to simply treat the depression
and thereby lower the risk of heart disease,
without understanding the exact pathway
between the two ailments?
That would make sense, except that
treating depression doesn't always appear to
improve cardiac health. "There's no strong
evidence that treating depression will
reduce the risk for heart attack," says
Scherrer. This is puzzling to researchers
because it seems to mock the wellestablished
notion that depression leads to
heart disease. And it makes them even more
determined to untangle the factors
connecting the two conditions.
Finkel cites a large, federally funded trial
that found that while cognitive behavioral
therapy modestly improved depression
symptoms in heart patients, it did little to
cut their risk of further cardiac incidents.
Treatment with the antidepressant drugs
known as SSRIs, however, reduced the risk
of a second heart attack or death by 42
percent.
SSRIs are known to make the blood less
likely to clot, and that could be part of why
they appear to exert some cardiovascular
benefit. "These drugs, independent of the
whole mood effect, seem to counterbalance
the tendency toward clotting," explains
Finkel.
However, there are also studies in which
even SSRIs failed to cut the heart risk for
depressed patients. In fact, in some trials the
drugs actually made things worse from a
cardiac standpoint. Regarding these studies,
Whooley notes: "The tough part is to sort out whether it's just
because the people on antidepressants have worse depression. It
may be that the worse the depression, the worse the cardiovascular
disease. And antidepressant use may just be a marker of worse
depression, rather than a mechanism between the depression and
the cardiac event."
Whooley's "Heart and Soul Study" suggests a different, less
invasive angle of intervention: Get people to exercise—a proven
remedy for depression and the heart. Says Scherrer, "Exercise is an
excellent prescription for all patients, including those with
depression."
Integrating physical and mental health care
Even though the mechanistic link between depression and
cardiovascular disease is still murky, and studies have thus far not
conclusively shown that treating depression helps the heart,
Scherrer and others say depression should be formally recognized
as a major cardiovascular risk factor. He says studies have shown it
to be at least as important as diabetes or hypertension in this
regard.
The American Heart Association's website acknowledges that
"individual response to stress" may play a role in heart disease but
stops short of listing depression as a full-fledged modifiable risk
factor.
Nonetheless, many cardiologists are realizing they need to be
more aware of depression's role in heart disease. And conversely,
according to Scherrer, psychiatrists should do more cardiovascular
screening. "Psychiatrists are fully trained medical doctors," he
says, "but how often do they pull out the stethoscope? Do they
ever check blood pressure? Why can't some basic screening be
incorporated into the treatment of psychiatric patients?"
VA may be ahead of most health systems in integrating mental
and physical care, notes Scherrer.
Patricia Dubbert, PhD, a psychologist and researcher at the G.V.
(Sonny) Montgomery VA Medical Center in Jackson, Miss.,
agrees. "In our hospital, we try really hard with our mental health
patients to make sure they're in primary care, which would do that
type of screening," says Dubbert. "But it is more difficult to get
some mental health patients into primary care, so that's where I
agree with the idea of bringing that type of screening into mental
health care. Wherever the patient will go, that's where we need to
provide the care." Ideally, she says, care should "be integrated in a
way that primary care providers have ready access to mental health
expertise and patients with mental illness
have ready access to primary care."
Part of the answer may lie in
collaborative care—an increasingly
popular model in VA.
The agency recently funded John
Rumsfeld, MD, PhD, of the Denver VA
Medical Center, to test a new model of
heart-failure care that emphasizes
multidisciplinary teams including a
primary care doctor, cardiologist and
psychiatrist. Managing depression will be
integral to the project.
Whether treating depression among the
VA patients in the study will ease their
heart burden—and reduce their risk of
dying—remains to be seen. But even
cardiologists are quick to point out that
helping patients cope with depression is
itself critically important.
Finkel: "We as cardiologists tend to be
very focused on whether the depression
treatment is going to improve survival. But
depression is a horrible disease. You really
see this when you take care of depressed
patients. It almost makes you cry."
This article originally appeared in the April 2009 issue of VA Research Currents.