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Lowered immunity puts older coronary bypass patients at higher risk for cognitive decline

Duke University Medical Center



Joseph Mathew, M.D.

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DURHAM, N.C. --- Older patients with lowered immunity to certain common bacteria found in the gastrointestinal tract are more likely than younger patients to suffer cognitive decline after coronary artery bypass surgery, according to a new analysis by Duke University Medical Center researchers.

The results of the Duke study were published today (Feb. 7, 2003) in the February 2003 issue of the journal Stroke.

Within the gut resides a class of bacteria known as gram-negative bacteria. These bacteria can release endotoxins into the bloodstream as a result of action of the heart-lung machine -- which circulates the blood throughout the body while surgeons operate on a stopped heart -- triggering a cascade of immunological events including systemic inflammation.

Since the machine does not circulate blood like the heart, the researchers said, the mucosal lining of the gut undergoes periods of low perfusion. During these periods, the gastrointestinal tract becomes more susceptible to bacteria crossing into the bloodstream.

Physicians can determine a patient's level of immunity to these bacteria by measuring the number of antibodies (EndoCAB) in the bloodstream that the body has created in response to the bacteria.

"In our study, we found that reduced preoperative levels of EndoCAB are a predictor of postoperative cognitive dysfunction in patients undergoing bypass surgery," said Joseph Mathew, M.D., Duke anesthesiologist and principal investigator of the study. "Among patients who undergo bypass surgery, low endotoxin immunity may exacerbate the inflammatory response typically associated with the heart-lung machine and cause greater cognitive dysfunction.

"This effect was particularly pronounced in patients over the age of 60," he said.

Each year, more than 750,000 patients worldwide undergo bypass surgery, and a 2001 Duke study published in the New England Journal of Medicine found that five years after such surgery, 42 percent of patients had measurable cognitive declines. In that study, age was found to be a predictor of cognitive decline, but the study was not designed to determine the reasons.

For the current study, the Duke team followed 460 patients, ranging in age from 23 to 87, scheduled to undergo elective bypass surgery. The researchers took EndoCAB measurements of each patient, and gave them a standard battery of cognitive tests just before surgery and then six weeks after. The tests measure such cognitive abilities such as short-term memory, attention, concentration, language comprehension, abstraction and spatial orientation.

Of all the patients, 36 percent suffered measurable cognitive decline six weeks after surgery.

"While we looked at many variables, EndoCAB level had a significant statistical interaction with age, indicating to us that the protective effect of EndoCAB is different in younger and older patients," Mathew explained. "Younger people have more robust immune responses, so they are better able to 'soak up' the endotoxins released as a result of surgery and negate their inflammatory effects."

Mathew said that strategies to boost immunity might have the potential to improve the outcomes of older patients. Therapies could include drugs that modulate the immune response or stimulate the production of the EndoCAbs, he said, adding that Duke will be one site of many involved in a clinical trial testing the effects of giving antibodies to older patients before surgery.

Last year, the Duke team reported that patients with lowered EndoCAB levels were more likely to suffer severe kidney damage as a result of bypass surgery. The researchers say that possible strategies used to protect the brain during surgery may also have a beneficial effect on renal function.

"We need to address the issue of cognitive decline because we are successfully operating on a progressively older and sicker group of patients," Mathew said. "While many of the complications of cardiac surgery have been minimized, cognitive decline is still one of the main areas that continued research can improve the quality of life for these patients."

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The researchers were supported by the National Institutes of Health.

Other members of the team, all from Duke, include: Hilary Grocott, M.D., Barbara Phillips-Bute, Ph.D., Mark Stafford-Smith, M.D., Daniel Laskowitz, M.D., Daniel Rossignol, Ph.D., James Blumenthal, Ph.D. and Mark Newman, M.D.

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