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For decades, heart disease has retained the dubious honor of being the leading killer of Americans. So doctors have long been on the lookout for potential new factors that could help them identify and protect people who are at high risk of the disease.

One such promising factor was homocysteine, a naturally occurring amino acid that previous studies have linked to a higher risk of heart events and stroke. But researchers in the U.K. now close the book on the usefulness of the marker, finding in a new study that lowering patients' blood levels of homocysteine did not in turn reduce their risk of heart trouble.

In the seven-year study of 12,064 heart-attack survivors, participants took daily supplements of folic acid and vitamin B12, which are known to break down homocysteine in the body. Although the supplementation lowered the amount of the amino acid in patients' blood 28%, it had no effect on rates of heart events or stroke compared with people taking placebo pills.

Researchers had believed that homocysteine, whose levels are determined by a combination of genetics and diet, affects a person's heart risk by damaging the lining of blood vessels and promoting the formation of blood clots. So scientists have been eager to determine whether controlled B-vitamin supplementation would result in a difference in heart-disease rates in patients. The new study shows that it did not, but some experts say they are not surprised by the findings, noting that previous studies had hinted that folic-acid supplementation has little effect on heart-disease outcomes.

"We've been through vitamin E, we've been through beta carotene, we've been through hormone-replacement therapy," says Dr. Alice Lichtenstein, director of the cardiovascular-nutrition laboratory at Tufts University, referring to some of the most recent candidates for reducing heart-disease risk. "Unfortunately, now we've been through folate."

Lichtenstein says it's not clear exactly why lower levels of homocysteine in the study did not translate to lower heart risk but notes that the findings cast doubt on the direct influence of the compound on heart disease. If homocysteine itself were directly harmful to the heart, then lowering its levels would have had some beneficial effect on death and disease rates in the study, which it did not. It's possible that homocysteine may instead be a marker for some other process that raises the risk of heart disease — one that is not influenced by folate. But the study was not designed to assess those mechanisms. "The only sound conclusion we can draw from this is that across the board, lowering of homocysteine with folate supplements does not result in improved cardiovascular outcomes," says Lichtenstein.

She adds that we should expect more studies exploring the role of homocysteine in heart disease; if it is a marker for some other unknown risk factor, further study may expose potentially new ways of treating or even preventing heart conditions.

• Alice Park