Ischemic stroke, the most common type of stroke, is caused by blood clots blocking blood flow to the brain. After accounting for other factors that affect stroke risk, researchers found the risk of stroke was more than four times higher in people with the highest homocysteine levels compared to those with the lowest levels.
"Population studies show that too much homocysteine in the blood is related to a higher risk of cardiovascular disease and stroke, so high homocysteine may be a marker of increased risk," says David Tanne, M.D., a stroke specialist at Sheba Medical Center and Tel Aviv University in Israel. "We add to this information by finding a strong graded association in patients already suffering from vascular disease."
Results of numerous studies suggest that high levels of homocysteine increase the risk of heart and blood vessel disease and ischemic stroke. How homocysteine increases risk is unclear, Tanne says. Some evidence indicates that it may damage blood vessels and predispose people to forming fatty deposits (atherosclerosis) and blood clots in arteries.
"A clear, direct causal link, hasn't been established yet," he says. "It remains to be demonstrated whether reducing high homocysteine levels will reduce the risk for heart disease and stroke."
The stroke-related impact of homocysteine in people with existing cardiovascular disease has not been studied extensively. To evaluate the issue, Tanne and his associates compared homocysteine levels in patients with stable coronary heart disease (CHD) and a matched control group. The CHD patients had previously participated in a study of cholesterol-lowering therapy.
Researchers reviewed hospital records and identified 80 CHD patients (of 3,090 who participated in the cholesterol-lowering study) who had ischemic strokes during more than eight years of follow-up and who also had complete information on homocysteine levels. Their average age was 61 and 95 percent were men. The patients were compared with 80 controls, who were matched according to age, gender and cholesterol-lowering therapy. Patients in the control group remained free of stroke or any recurrent event throughout the study.
Overall, the stroke patients had higher homocysteine levels, reflected by a median value of 16.4 micromoles per liter (umol/L), compared to 14.3 umol/L in the control group. Additionally, two-thirds of the stroke patients had higher homocysteine levels than their matched controls.
"Our findings . . . are consistent with a strong predictive role of [homocysteine] levels, independent of traditional risk factors or inflammatory markers, for incidence of ischemic stroke in patients at increased risk due to pre-existing coronary heart disease," the researchers concluded.
The benefits of lowering homocysteine levels remain unproven, but Tanne notes that dietary changes and vitamin intake are an effective, inexpensive way to reduce homocysteine levels. Consuming more folic acid and vitamin B12 have been shown to reduce homocysteine levels.
"Patients suffering from vascular disease should keep a healthy, balanced diet," he says. "Citrus fruits, tomatoes, vegetables and grain products are good dietary sources of folic acid."
He adds that several ongoing studies in the United States and Canada are evaluating the impact of homocysteine-lowering therapy on stroke and other cardiovascular diseases.
Co-authors are Moti Haim, M.D.; Uri Goldbourt, Ph.D.; Valentina Boyko; Ram Doolman; Yehuda Adler, M.D.; Daniel Brunner, M.D.; Solomon Behar, M.D.; and Ben-Ami Sela, Ph.D.
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