Sep. 22, 1999 DALLAS, Sept. 21 -- More evidence has been found linking a condition called hemochromatosis, a disorder that allows too much iron to be absorbed from food, to an increased risk of heart attack and stroke.
In today's Circulation: Journal of the American Heart Association, two independent research teams found that people with an iron-regulating mutation (a defect) had a much higher risk of having and dying from a heart attack. The research builds on earlier studies that have shown that individuals with elevated levels of iron are at higher risk for heart disease. The explanation for this association is not known.
Hemochromatosis is an inherited disease in which individuals absorb too much iron in the liver and other organs of the body, such as the heart or pancreas, and die from liver cirrhosis, liver cancer and heart failure. The mutation for the most common form of hemochromatosis was identified in 1996. The disease occurs in individuals who have inherited two mutated copies, one from each parent, of the hemochromatosis gene. The new research examines whether individuals who have only one mutated gene, and are called "hemochromatosis carriers," are at increased risk for heart disease and stroke.
A new genetic test that is now available offers scientists a more precise method for determining if carriers of the gene mutation are at increased risk for heart disease. Researchers needed a genetic test to study carriers of the gene. Carriers often have a small elevation in their iron storage levels that may be responsible for the observed increase in heart attacks. Carriers are rarely aware of their status and usually have no symptoms until a heart attack or stroke occurs.
In an accompanying editorial, Jerome L. Sullivan, M.D., Ph.D., clinical assistant professor at the University of Florida in Gainesville, writes that these authors "present landmark studies" on the link between iron and coronary heart disease.
Still, he emphasizes that "many important unresolved questions" remain. Sullivan, who proposed a link between iron and coronary disease nearly 20 years ago, says that the evidence accumulated so far seems to support voluntary blood donation as a means of depleting iron stores in the body. However, he adds, that, "A consensus is urgently needed on public health recommendations. But based on what we know now, a strong case could be made for recommending blood donation as a way to lower iron levels, thus lowering heart attack risk." Although the American Heart Association believes research involving the hemochromatosis gene mutation raises some interesting questions, further study is needed before the organization could make widespread recommendations concerning screening for the defective gene or risk-reduction methods for those who are found to carry the hemochromatosis gene mutation. It is estimated that one in 10 individuals are carriers of the mutation.
Traditionally, it was thought that someone who carried the gene wouldn't have heart disease and other problems of iron overload. But according to these studies, carriers of the defective gene are at increased risk. One in 200 have both genes whereas one in 10 are carriers.
In the Dutch study, women who carried the gene had double the risk of dying from a heart attack or stroke death. Women who smoked, had high blood pressure and were carriers of the mutated gene had nearly 19 times the risk of heart attack and stroke death compared to non-smokers with normal blood pressure level who were not gene carriers, says to Mark Roest, M.Sc. of the Utrecht University Medical School in the Netherlands.
"This is the first large study to find a significant association between women who are carriers of the gene and cardiovascular disease," he says. The study also offers additional support for the so-called iron hypothesis and how it might explain why many women are protected from coronary heart disease until menopause. The iron hypothesis says that iron depletion protects individuals against heart disease, whereas excess levels of iron increase the risk. Many scientists believe that premenopausal women are protected from heart disease, at least in part, because their iron reserves are depleted each month during menstruation.
Researchers studied 12,239 middle-aged women living in Utrecht, Netherlands. The women were followed for 16 to 18 years. "Testing for the hemochromatosis gene may play a critical role in predicting a postmenopausal woman's risk for cardiovascular death," says Roest.
In the study in Finland, researchers looked at the prevalence of the hemochromatosis gene among 1,150 Finnish men who were participants in the Kuopio Ischemic Heart Disease Risk Factor Study. Previously, the same Finnish team published in 1992 the first evidence in favor of the role of iron accumulation in coronary disease.
"Carriers of the gene have more than twice the risk for a heart attack compared to non-carriers," says the study's senior author, Jukka T. Salonen, M.D., Ph.D., of the University of Kuopio in Finland. The Finnish scientists believe that the hemochromatosis gene mutation is a new explanation for the exceptionally high occurrence of coronary disease in eastern Finland.
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