Researchers Take A Second Look At Homocysteine's Link To Heart Disease

Previous studies have found a strong association between elevated blood levels of homocysteine and heart disease, suggesting a causal relationship.

However, in a study reported in today's Circulation: Journal of the American Heart Association, researchers did not find a causal relationship between homocysteine and risk of heart disease. Instead, scientists showed that vitamin B-6 was a better indicator for heart disease risk. People who had the highest blood levels of vitamin B-6 had about one-third the risk of developing heart disease when compared to people with the lowest levels of vitamin B-6.

Researchers used frozen blood samples to determine levels of homocysteine and B vitamins -- which can reduce homocysteine levels -- in 759 people from 45 to 64 years of age who participated in the Atherosclerosis Risk in Communities (ARIC) study.

The study participants were initially evaluated during a three-year span from 1987 to '89. Most of the participants were reexamined between 1990 and '92 and again between 1993 and '95. During the study, 232 people developed heart disease.

"I believe that homocysteine isn't as important as some previous research suggests and that more studies are needed to clarify how homocysteine, B vitamins and heart disease are linked," says Aaron Folsom, M.D., of the University of Minnesota and lead author of the study. Folsom and his colleagues report that homocysteine is elevated after a heart attack or cardiac arrest, rather than before it.

Folsom points out the difference between his study and previous research that links elevated homocysteine with heart disease: Unlike other investigations, his study was prospective -- it took a random sample of people who had not been diagnosed with heart disease and followed them over time to determine whether any of them would develop heart disease. Other studies, that may have misrepresented the importance of homocysteine, evaluated people who already had a heart attack or developed atherosclerosis, says Folsom.

An accompanying editorial by Lewis H. Kuller, M.D., and Rhobert W. Evans, Ph.D., from the University of Pittsburgh, states, "A decrease in B vitamins is the primary cause of the increased risk of vascular disease. Elevated levels of homocysteine may just be a marker of low vitamin levels," rather than a cause of atherosclerosis, the fatty obstructions in blood vessels that can cause a heart attack.

Kuller adds, "At the present time we're not really sure whether elevated homocysteine is really a risk factor for heart disease or whether lowering homocysteine by increasing folic acid or B vitamins will reduce risk." He says more prospective studies and clinical trials of B vitamins should be done to determine their real importance in preventing heart disease. Co-authors of the study were F. Javier Nieto, M.D., Ph.D.; Paul G. McGovern, Ph.D.; Michael Y. Tsai, Ph.D.; M. René Malinow, M.D.; John H. Eckfeldt, M.D., Ph.D.; David L. Hess, Ph.D.; and C. E. Davis, Ph.D.