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Gene Test Could Catch Deadly Heart Problem
Date:7/31/2008

Tear in the aorta is unpredictable and often fatal, researchers say,,

THURSDAY, July 31 (HealthDay News) -- A series of genes linked to acute aortic dissection could lead to a rapid diagnostic test for this often fatal problem, German researchers report.

Acute aortic dissection is a tear in the lining of the aorta, the artery that carries blood from the heart to the rest of the body. About 2,000 people a year in North America suffer an acute aortic dissection, according to the American Heart Association.

"Thirty-three percent of acute aortic dissection patients die within the first 24 hours if they remain untreated because the disease is not diagnosed," lead researcher Salah A. Mohamed, from the Department of Cardiac Surgery at the University of Schleswig-Holstein said in a statement.

The report was presented Wednesday at the American Heart Association's Basic Cardiovascular Sciences Conference, in Keystone, Colo.

In the study, Mohamed's team looked at samples of aorta tissue from 19 patients who had acute dissection. These patients had no known connective tissue disease.

The samples were compared with samples from eight patients who had a mutant gene for Marfan syndrome, a disease that affects connective tissue, which in turn makes blood vessels weak. The researchers also compared tissue from six patients who had undergone heart valve replacement.

In all the patients who had acute aortic dissection, the researchers found 88 genes that were significantly different from the same genes in Marfan patients and in patients who had undergone heart valve replacement.

In addition, Mohamed's group found that a protein called MS FBN1 interacted with the proteins of four of the 88 genes, namely, fibulin 1 (FBLN1), fibulin 2 (FBLN2), Decorin (DCN), and microfibrillar associated protein 5 (MFAPS5).

All of these proteins are involved in building tissue that surround the cells in the aorta. Moreover, one of the four is involved in the development of Marfan syndrome, Mohamed noted.

The researchers found that two of the genes were overexpressed by at least threefold, and two were underexpressed by threefold. The underexpressed genes may explain the cause of acute aortic dissection, the researchers noted.

"We did our study primarily to gain a better understanding of the molecular mechanism underlying acute aortic dissection," Mohamed said.

"The study was also aimed at the future development of a clinical test for monitoring patients with a high risk of acute aortic dissection. Most acute aortic dissection patients do not have a known connective tissue disorder. The identification of the four genes could be a starting point to develop a diagnostic tool," Mohamed said.

Acute aortic dissection is usually accompanied by chest pain that may radiate to the back. Other symptoms include nausea, sweating and difficulty breathing. These symptoms can be easily confused with a heart attack.

Dr. Curtis Rimmerman, the Gus P. Karos Chair of Clinical Cardiovascular Medicine at Cleveland Clinic, noted that aortic dissection is a life-threatening condition with high morbidity and mortality rates, and it is most often an unpredictable event.

"Any genomic advance that may be able to identify those patients with a heightened risk for acute aortic dissection represents a significant positive step forward," Rimmerman said.

With the exception of those patients with Marfan syndrome and those with a family history of aortic dissection, no screening program is in place to identify patients at risk for aortic dissection, Rimmerman said.

"Should those patients predisposed to aortic dissection be reliably identified, this would permit heightened attention to lifestyle modification, blood pressure control, and the preemptive administration of certain medications such as beta blockers," Rimmerman said. "Additionally, in those patients identified as high-risk, this would undoubtedly involve focused efforts at aortic imaging," he said.

Rimmerman cautioned, however, that this was a small study and would need to be replicated in a larger patient group before such testing could be ready for clinical use.

More information

For more on aortic dissection, visit the American Heart Association.



SOURCES: Curtis Rimmerman, M.D., Gus P. Karos Chair, Clinical Cardiovascular Medicine, and staff cardiologist, Cleveland Clinic, Ohio; July 30, 2008, presentation, American Heart Association's Basic Cardiovascular Sciences Conference, Keystone, Colo.


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