Heredity Cuts Both Ways With Heart Disease

Family history can hurt, good gene can help

TUESDAY, May 11, 2004 (HealthDayNews) -- The potentially good and bad effects of inheritance on the risk of heart attack and stroke emerge from two studies an ocean apart.

In the United States, researchers at the long-running Framingham Heart Study report that people whose parents had cardiovascular problems relatively early in life are more likely to have a heart attack or stroke in their adult years.

From Italy comes a report that people who have one version of a gene for the molecule cox-2 have a lower risk of heart attack and stroke than those with other forms of the gene.

Both studies appear in the May 12 issue of the Journal of the American Medical Association.

One surprising aspect of the Italian report is that cyclooxygenase 2, to give it its formal name, has been of enormous interest because of its role in pain. It is the target of Celebrex and other well-known painkillers, but has rarely been linked to cardiovascular disease.

The Italians speculate the specific version of the cox-2 gene lowers risk by reducing inflammation that can cause a fatty plaque in the lining of an artery to burst, blocking the blood vessel.

The study compared 864 people who suffered heart attacks or strokes between March 2002 and October 2003 to 864 people hospitalized for other reasons. It found people who did not have a heart attack or stroke were 2.4 times more likely to have the protective version of the cox-2 gene.

"This provides a provocative hypothesis that variations in genes involved in inflammation may play a role in susceptibility to heart attack and stroke," said Dr. Christopher J. O'Donnell, associate director of the Framingham Heart Study and lead author of the American report.

That report is based on data about more than 2,300 people in the study, which has been funded by the National Heart, Lung, and Blood Institute since 1971.

Someone with at least one parent who had cardiovascular disease relatively early -- before age 55 in men and 65 in women -- was 2.6 times more likely to have a heart attack or stroke than offspring whose parents did not have early disease, the researchers found.

The finding adds information to support the current recommendation that doctors ask about family history of heart attack and stroke when assessing a person's risk, O'Donnell said.

"While questions about family history are part of the standard, the truth is that there has been limited information about how to use that parental data," he said. "This is the first large study with actual data, where we knew exactly what happened to parents and offspring."

The study points to a group of people who should be given special attention, O'Donnell said, those with a parental history of cardiovascular disease and moderate elevation of known risk factors, such as blood pressure and cholesterol. The risk was high for those people in the Framingham group.

The Italian study casts some light on the reason for that heightened risk, O'Donnell said: "It suggests that some of the unexplained risk from a family history might be explained by new pathways. It kind of fits into the paper we have."

But the cox-2 link to heart attack and stroke "is not ready for clinical use," he said. "It needs to be confirmed by findings in other diverse populations."

The Italian study provides more evidence that "inflammation plays an important role in a spectrum of diseases ranging from heart disease to cancer," said Dr. Andrew J. Dannenberg, a professor of medicine at Weill Medical College of Cornell University who has done research on the role of cox-2 in cancer.

"A key point is that chronic inflammation is a common component in a variety of diseases of aging," Dannenberg said. "That raises hopes for pharmaceutical approaches that target inflammation."

While there is evidence that cox-2 inhibitors such as Celebrex "might have anticancer properties, and some evidence that it may be of benefit in cardiovascular disease," more work is needed to establish if they have a place in treatment, he said.

"We have to await the results of prospective trials to know if they would be of benefit," Dannenberg said. Some trials are under way, he added.

More information

A summary of what is known about family history and heart disease is available at the American Heart Association, which also has a page explaining other risk factors.

SOURCES: Christopher J. O'Donnell, M.D., associate director, Framingham Heart Study, Framingham, Mass.; Andrew J. Dannenberg, M.D., professor of medicine at Weill Medical College, Cornell University, New York City; May 12, 2004 Journal of the American Medical Association
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