Duke Researchers Uncover Genetic Link To Stroke After Heart Surgery

Furthermore, since the two implicated genes are involved in the body'simmune response to insult or injury, the researchers said that theirfindings strongly suggest that inflammation plays an important role inpost-operative stroke.

The researchers said that if the findings are confirmed by moreextensive studies, they could become part of a battery of genetic teststo better identify the risk to patients of stroke after surgery.

"Despite all our advances in improving outcomes after cardiac surgeryover the decades, stroke remains a significant and debilitatingcomplication," said Duke cardiothoracic anesthesiologist HilaryGrocott, M.D., whose study results were published early on-line in thejournal Stroke. The study was supported by the National Institutes ofHealth and the American Heart Association.

"As the population of patients getting cardiac surgery continues toage, it is important for us to better understand all the factors thatimpact mortality and the quality of life for these patients," hecontinued. "Discovering that these two genes are linked to stroke afterheart surgery is an important first step that should now be validatedby larger studies."

While it is still too early to change clinical practice basedon the findings of the Duke team's findings, Grocott said that in thenot-too-distant future physicians will be better able to define aspecific patient's risk for adverse outcomes after heart surgery basedon a spectrum of genetic and clinical information.

"When discussing the risks and benefits of surgery, it is important topatients to know whether they are at a higher or lower risk," he said.

For their study, the researchers selected 26 genes implicatedin past non-surgical studies as possibly playing a role in theincidence of stroke. The genes identified regulate three generalprocesses -- coagulation, inflammation and lipid metabolism.

After identifying the candidate genes, the researchers thenconsulted a databank of 1,635 patients enrolled in an ongoing Dukestudy on the role of genetics in cardiac surgery outcomes. Of thosepatients, 28 (1.7 percent) suffered a stroke after surgery. Nationally,the reported incidence of stroke after heart surgery is approximatelytwo percent but can vary widely, Grocott said.

The researchers then analyzed blood samples to determine whetherspecific variants, known as polymorphisms, of the 26 candidate genes,either alone or in various combinations were associated with stroke.

While they found that no individual polymorphism was linked to stroke,the team did find that patients with a specific combination ofpolymorphisms in genes responsible for the production of C-reactiveprotein (CRP) and interleukin-6 (IL-6) suffered stroke at more than athree times higher rate. CRP is a protein released into the bloodstreamas a natural reaction to infection, fever or other injury, while IL-6is a protein that regulates the intensity of the immune response.

Of the patients enrolled in the study, 36 percent had thepolymorphism pair in question -- 3.09 percent of those patientssuffered a stroke, while only 0.95 percent of patients without the pairsuffered a stroke.

"We know that a patient's genetic makeup plays a major role in so manydiseases, there's no reason to believe that cardiac surgery is anydifferent," Grocott said. "We also know that cardiac surgery is one ofthe biggest pro-inflammatory stimuli known, so the fact thatinflammation is involved is not surprising."

While the role of inflammation was not surprising, Grocott said theteam found it significant that they found no links to genes involved inthe blood coagulation pathway. "To see these patients get strokeswithout a thrombotic polymorphism is somewhat of a novel finding initself," he continued.

Grocott said that since this polymorphism pair appears to be present inmore than one-third of the population undergoing heart surgery, furtherstudy is needed not only to better understand the underlying mechanismsinvolved but to determine if new approaches to minimize theinflammatory response in patients identified at high risk could impactoutcome.

Two earlier Duke studies this year have found genetic links to otheradverse outcomes after cardiac surgery. One study found polymorphismslinked to kidney damage after heart surgery (http://www.dukemednews.org/news/article.php?id=8428),while another study uncovered polymorphisms that can help predict whichpatients are more likely to suffer bleeding episodes after heartsurgery (http://www.dukemednews.org/news/article.php?id=8658).

Other members of the team, all from Duke, are: William White, RichardMorris, Ph.D., Mihai Podgoreanu, M.D., Joseph Mathew, M.D., DebraSchwinn, M.D., and Mark Newman, M.D. Dahlia Nielsen, Ph.D., now at N.C.State University, was also a member of the team.

All of the researchers are members of the Perioperative Genetics andSafety Outcomes Study (PEGASUS), an ongoing longitudinal andprospective study whose goal is improving the outcomes of cardiacsurgery.