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DURHAM, N.C. -- Variants of two genes involved in the
inflammatory system appear to protect patients from suffering a
decline in mental function following heart surgery.

Duke University Medical Center researchers believe their
findings could help physicians identify patients at risk of
suffering mental decline after heart surgery and raises the
possibility that these patients could be treated with drugs
that are known to dampen the inflammatory response.

Six years ago, the Duke researchers demonstrated that 42
percent of patients who underwent coronary artery bypass
surgery had measurable cognitive decline five years after their
procedure. Since that finding, the team has been investigating
possible reasons for this decline.

The researchers selected known variations in 37 genes that
previous studies had implicated in various impairments of
cognitive and mental function. When they looked at more than
500 heart surgery patients and correlated cognitive decline
with the patient's genetic makeup, they discovered that
patients with two specific variants were less likely to have
problems with areas of cognitive function such as memory,
attention and concentration.

"While bypass surgery has saved millions of Americans with
coronary artery disease, many patients and families find that
cognitive decline after surgery has reduced their quality of
life," said Duke cardiothoracic anesthesiologist Joseph Mathew,
M.D., lead investigator of the study reported online Tuesday,
May 1, in the Journal of the American College of Cardiology.
The study was supported by the National Institutes of Health
and the American Heart Association.

"The two gene variants we found were involved in some manner
with the inflammatory system, raising the possibility that
therapies given during surgery aimed at the controlling the
inflammatory response would be protective," Mathew said. "Also,
our results provide additional evidence for a genetic basis for
the cognitive deterioration seen after heart surgery."

The researchers found that patients with variants in genes
for C-reactive protein and P-selectin were less likely to
suffer cognitive decline than were patients without the
variants. C-reactive protein plays an important role in the
body's initial response to injury, and studies have shown that
high levels of the protein put patients at higher risk for
cardiovascular disease and stroke. P-selectin is a molecule
that helps recruit circulating white blood cells to the site of
an injury.

For their analysis, the researchers gave 513 heart patients
at Duke University Hospital a battery of cognitive exams before
heart surgery and then six weeks later. They found that
patients with the variation of the C-reactive protein gene were
20.6 percent less likely to suffer mental decline, and patients
with the P-selectin variant had a 15.2 percent risk reduction.
The incidence of deficit in patients with both gene variants
was 17 percent compared to 43 percent in patients who had
neither variant.

Furthermore, patients with the two gene variants had
significantly lower levels of C-reactive protein in their
bloodstream and lower P-selectin expression, and the
researchers said this factor may provide a biological basis for
the protective effect they observed.

"Although we have made significant progress in minimizing
the adverse events related to cardiac surgery, little progress
has been made in reducing postoperative cognitive decline,"
said Mark Newman, M.D., chairman of anesthesiology and senior
member of the research team. "While we know that there are many
factors involved in this phenomenon, the results of this study
provide insight into the genetic factors that influence
cognition and may translate into more precise identification of
at-risk patients."

Coronary artery bypass grafting surgery is performed more
than 600,000 times a year in the United States for the
treatment of coronary artery disease. Typically, surgeons use
pieces of blood vessels from other parts of the body to
"bypass" clogs in coronary arteries, thereby restoring blood
flow to the heart.

Other Duke members of the team were Mihai Podgoreanu, Hilary
Grocott, William White, Richard Morris, Mark Stafford-Smith, G.
Burkhead Mackensen, James Blumenthal, and Debra Schwinn.
Christine Rinder, of the Yale University School of Medicine,
also was a team member.