Homocysteine Linked to Heart Failure

"Normal" Levels in Women Riskier Than Those in Men

March 11, 2003 -- High blood levels of the amino acid homocysteine appear to be associated with a greater risk of heart disease and stroke, but they may be a much stronger predictor of heart failure. New research from the ongoing Framingham Heart Study shows that people without previously known heart disease who have high homocysteine levels had double the risk of congestive heart failure than those with low levels.

Many questions remain about the value of homocysteine as a marker for heart and vascular problems. Study results seem to have dashed the hope that homocysteine would prove as critical as cholesterol or blood pressure in predicting heart disease, but there is still hope that lowering homocysteine levels with folic acid and vitamins B6 and B12 can impact risk. Another unanswered question: What constitutes "normal" and "high" homocysteine levels? The new research suggests that women with homocysteine levels that are generally considered to be normal may have an increased risk of heart failure.

"People with heart failure tend to have elevated levels of homocysteine and there is growing evidence that the heart is susceptible to homocysteine-induced injury," lead researcher Ramachandran S. Vasan, MD, tells WebMD. "That is why we looked at this. We wanted to see if the association with heart failure was stronger than with cardiovascular disease, coronary disease, or stroke."

As many as 3 million Americans suffer from heart failure, and 400,000 new cases are diagnosed each year. The condition occurs when the heart loses its ability to pump blood efficiently through the body, often due to an underlying problem such as heart disease, high blood pressure, or a prior heart attack. Risk increases with age -- about 5% of 75-year-olds have some degree of heart failure -- and blacks have twice the risk of dying from heart failure as whites.

The new study, reported March 12 in TheJournal of the American Medical Association, included almost 2,500 people who were at elevated risk for heart failure because of their age, but had no evidence of heart failure and had no prior heart attacks. Participants were divided into four groups by homocysteine level.

Vasan says men and women in the top two homocysteine groups were twice as likely to develop heart failure as those in the bottom two groups. Women with the highest levels had four times the heart failure risk as women with the lowest levels, and the risk doubled for women with the second to lowest levels.

"The homocysteine-related risk seemed to increase steadily in women, but we did not see this in men," Vasan says. "The risk for women with homocysteine levels that are considered normal was double that of women with the lowest levels. Women have a lower baseline risk of heart failure than men and this may have something to do with it. But this association definitely needs more study."

The Framingham researchers concluded that further studies should assess whether heart failure risk can be reduced by lowering homocysteine levels with folic acid and vitamins B6 and B12. No fewer than 20 prevention studies are under way to answer this question with regard to heart disease, and findings from some of them should be made public soon.

National Heart Lung and Blood Institute epidemiologist Teri Manolio, MD, PhD, says even without the studies the question of whether folic acid reduces the risk of heart disease and heart failure may soon be answered because enriched grain products are now fortified with the vitamin. Fortification began several years ago in an effort to lower the incidence of neural tube birth defects like spina bifida. Manolio is director of the NHLBI's epidemiology and biometry program.

"We have already seen a shift in folic acid levels within the general population, with the lowest levels all but disappearing," Manolio tells WebMD. "We don't know what impact this will have on cardiovascular risk, but we may know more in a few years."

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SOURCES: The Journal of the American Heart Association, March 12, 2003. Ramachandran S. Vasan, MD, associate professor of medicine, Boston University School of Medicine; investigator for the NHLBI's Framingham Heart Study. Teri Manolio, MD, PhD, director of NHLBI Epidemiology and Biometry Program.
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