Two Studies: Long-Term Cognitive Decline After Bypass Surgery; Alzheimer's Gene Linked to Earlier Bypass
CHICAGO, IL -- How well a patient responds to heart bypass
surgery may depend as much on the brain as the heart. In two
studies, researchers from Duke University Medical Center have
shown that heart surgery can affect mental functioning, and
that a gene involved in a brain disease may predispose patients
to early surgery.
One study concluded that although coronary artery bypass
graft (CABG) surgery is intended to improve blood flow to the
hearts of more than 600,000 Americans each year, it is less
beneficial to the brains of some of those patients. One-third
of the patients studied had measurable cognitive declines five
years after surgery, and the researchers suspect that is due to
the use of the heart-lung machine.
Another study found that having a common gene that
predisposes people to Alzheimer's disease may predict early
heart problems. In the Duke study, patients with the APOE-4
gene received surgery up to10 years earlier than the population
as a whole.
The results of the Duke studies were prepared for
presentation today (April 26) by Dr. Mark Newman, chief of
cardiothoracic anesthesia, during a poster session at the
annual meeting of the Society
for Cardiovascular Anesthesiologists.
Both studies were supported by grants from the National
Heart, Lung and Blood Institute (part of the National
Institutes of Health) and the American Heart Association.
Cognitive decline after bypass surgery
Duke researchers, like other physicians, have been aware
that CABG surgery can cause mental dysfunction in some
patients. To find out just how many patients are affected, they
designed a test that each patient took before surgery, at
discharge, at six weeks and five years following surgery. The
test assessed such factors as memory, concentration and
To their surprise, the researchers concluded that after a
five-year follow-up of 313 patients, nearly one-third (31.1
percent) of these patients had measurable cognitive
"Little is more devastating than for patients and their
families to have a successful operation that prolongs life, but
diminishes the quality of that prolonged life," Newman said.
"Our results confirm long-term persistence of cognitive
dysfunction and the importance of prevention of these
It is highly likely that the source of the problem is the
heart-lung bypass machine commonly used in CABG surgery, Newman
said. This machine essentially acts as the body's heart and
lungs while surgeons operate on the stopped heart.
"While we have known for some time that the heart-lung
machine is probably a cause, we don't know for certain exactly
what the mechanism is," Newman said. "It is likely that tiny
emboli, or clots, are formed and travel to the brain. Other
factors, such as inflammation and the lowered blood pressures,
could play a part as well.
"There needs to be further investigation into operative
neuroprotection to allow us to reduce the short- and long-term
consequences of cognitive decline after surgery," Newman said.
One of the ways heart surgeons are trying to lessen the impact
of CABG surgery is to perform the surgery on a beating heart,
which doesn't require the heart-lung machine, though it
presents technical challenges of its own.
"As in everything in medicine, you must balance the benefits
with the risks," Newman explained. "By operating on a beating
heart, you don't need a bypass machine; however, you must
factor in whether or not the quality of the suturing and
connections, and the additional time in the operating room,
would be the same as the conventional approach."
Joining Newman in the study were Jerry Kirchner, Barbara
Phillips-Bute, Elizabeth Phillips, Duke Han, Bruno Baudet, Dr.
Alina Grigore, Dr. J.G. Reves and James Blumenthal, all from
The Alzheimer's gene link to heart disease
The gene apolipoprotein (APO) comes in three variants, E-2,
E-3 and E-4. Researchers have known that not only is the E-4
variant linked to Alzheimer's disease, but that it is a risk
factor for the development of atherosclerosis, the buildup of
plaques within coronary arteries that cause heart disease.
Since the APO gene is involved in the regulation of cholesterol
and triglycerides in the blood, it is believed the E-4 variant
leads to a buildup of these lipids, high levels of which are
considered risk factors for heart disease.
The Duke study was the first to look at the relationship
between APOE-4 status and the timing of a patient's first CABG
surgery, Newman said. Based on a genetic analysis of 576 CABG
patients, the researchers found that those with the APOE-4
variant were much younger when they received their
"We found a significant difference in the average age at
surgery between people who have the variant gene and those who
don't," Newman said. "While there are probably other factors
involved, APOE-4 status appears to be an important determinant
of when a heart patient receives bypass surgery."
The average age for CABG surgery in the general population
is 65. However, the Duke study found that patients who
inherited a copy of the defective gene from one parent got the
operation at the average age of 60.6. Those who inherited a
defective copy from each parent received the operation at the
average age of 54.2.
Although the APOE-4 link is statistically significant,
Newman said, the mechanisms underlying the association are
still unclear. He does believe, however, that APOE-4 is
involved somehow in the inflammation process that can occur
when a plaque ruptures or is damaged.
"When a plaque ruptures, platelets in the blood arrive at
the scene of the injury and clots can form, which can lead to
an acute cardiac event," Newman said. "It may be that in people
with the E-4 variant, these plaques are more susceptible to
rupture or other injury."
While a simple genetic test can help physicians spot
patients who might be at risk for heart disease, Newman said it
is still too early for these findings to be translated into a
drug or treatment that can be used to treat heart patients.
However, since many researchers are already investigating the
role of APOE-4 in Alzheimer's disease and stroke, a potential
treatment might not be that far away, Newman said.
To better understand the genetics behind heart disease,
Newman and his team plan to collect genetic samples from all
consenting CABG surgery patients at Duke.