High Homocysteine Concentrations In Blood Warn Of Increased Heart Attack Risk In Young Women

July 14, 1997

DALLAS, July 15 - A twofold increased risk of heart attack was found among women who have higher than normal blood levels of the protein homocysteine and lower than normal blood levels of the vitamin folate, according to a study in today's American Heart Association journal Circulation.

The new study, the first to investigate homocysteine as a risk factor in a large number of young women, provides evidence that high homocysteine may indicate increased heart attack risk, says lead author Stephen M. Schwartz, Ph.D.

Homocysteine, a product resulting from the metabolism of an amino acid methionine, is known to damage blood vessels, increasing the potential for cholesterol buildup in the bloodstream.

Schwartz, associate professor of epidemiology at the University of Washington School of Public Health in Seattle, and his colleagues assessed homocysteine in women 18 to 44 years of age, almost 90 percent of whom were non-Hispanic whites. They interviewed and obtained blood samples from 79 women who had suffered a heart attack between July 1, 1991, and Feb. 28, 1995. As a control group, they used 386 women without coronary heart disease of the same age. All the study participants lived in Seattle's Washington's King, Pierce, or Snohomish counties.

Blood concentrations of total homocysteine, folates and vitamin B12 were determined. Because genetic factors also contribute to homocysteine, researchers measured a specific type of gene called MTHFR that helps regulate homocysteine. Other researchers had found that individuals who have a mutation on the gene have higher homocysteine levels.

Women in the top 10 percent of total homocysteine measurements had 2.3 times the heart attack risk of women in the lowest 50 percent. Women who had high homocysteine levels tended to have low folate levels and vice versa. The researchers found no difference in vitamin B12 concentration between heart attack survivors and the controls, and "little relationship between B12 concentration and heart attack risk."

Researchers took into account factors such as age, diabetes, cigarette smoking and obesity.

This risk was actually lower than reported in the few small studies that had investigated homocysteine in women. This may have stemmed from the high influence of cigarette smoking and obesity, factors that are quite common among the heart attack cases and probably played a big role in causing their heart attacks, Schwartz says.

Women who carried two copies of the mutated gene tended to have a 25 percent or greater level of homocysteine than women with two copies of the standard MTHFR gene, a finding consistent with other studies. However, this held true only for those women who had low folate concentrations. This further fuels the question of the relationship between folic acid intake and homocysteine levels and what role the mutated gene may play in modifying it.

Interestingly, the Seattle study did not find that having two copies of the MTHFR gene variation increased a woman's risk of heart attack. The authors note that similar findings have emerged from the majority of recent studies of the MTHFR mutation and coronary heart disease, although three studies have reported a two to threefold increased risk for people with two copies of the mutated gene.

The reasons for these discrepancies are not clear, but Schwartz says that carrying double copies of the mutated gene may only increase the risk in people who fail to consume adequate folic acid. They urge a major study to determine the inter-relationship of B vitamin supplementation, genetic factors and homocysteine on the risk of cardiovascular disease.

Studies have shown that B vitamin supplements reduce the blood's concentrations of homocysteine, but no major study has yet addressed whether lowering homocysteine concentrations actually reduces cardiovascular risk.

"Our study adds support to the need for randomized trials to determine whether supplementation with folates (folic acid) and other B vitamins, such as B6 and B12, can prevent cardiovascular disease." Good sources of folic acid include orange juice, breakfast cereals, and fruits and vegetables. Vitamin B6 can be obtained from red meat.

The Seattle-area study also found, as other studies have, that women who inherit two mutated copies of the gene MTHFR had higher blood homocysteine concentrations. However, inheriting this common gene variation, which occurs in 10-13 percent of whites, did not in itself increase the risk of heart attack.

"Particularly among young women, we had expected that genetic factors would have played a stronger role in the relationship between homocysteine and heart attack risk," Schwartz says. "That we didn't see that was surprising."

In recent years, a growing body of evidence has linked high homocysteine to heart attacks, strokes, and other cardiovascular diseases. The all-male Physicians Health Study found that high homocysteine level increased the risk of heart attack 3.4 times. A study by Cleveland Clinic researchers found high homocysteine levels increased the heart attack risk among older men and women, particularly those over age 65. Among older people in the Framingham (Mass.) Heart Study, 21 percent had homocysteine levels that put them at increased risk of heart attack.

"Particularly among young women, we had expected that genetic factors would have played a stronger role in the relationship between homocysteine and heart attack risk," Schwartz says. "That we didn't see that was surprising."

A Dutch team reported in the May issue of the AHA journal Arteriosclerosis, Thrombosis and Vascular Biology that every 10 percent rise in homocysteine in its study participants was matched by almost the same increase in coronary heart disease risk.

Other co-authors of the report are David S. Siscovick, M.D.; Frits R. Rosendaal, M.D., Ph.D.; R. Kevin Beverly, M.S.; Bruce M. Psaty, M.D., Ph.D.; W. T. Longstreth, Jr., M.D. and Thomas D. Koepsell, M.D., of the University of Washington; M. Rene Malinow, M.D. and David L. Hess, Ph.D., of the Oregon Regional Primate Research Center, Beaverton; T. E. Raghunathan, Ph.D., of the University of Michigan, Ann Arbor; Frits R. Rosendaal, M.D., of the Leiden University, Leiden; and Pieter H. Reitsma, Ph.D., now at the Academic Medical Center, Amsterdam.

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Media advisory: Dr. Schwartz can be reached in Seattle by calling (206) 287-2777 or via e-mail: stevesch@u.washington.edu (Please do not publish telephone numbers.)

American Heart Association

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