Reducing homocysteine levels does not prevent stroke recurrence
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《英国医生杂志》
Among patients with a previous stroke, reducing levels of the amino acid homocysteine in the blood with high dose vitamin therapy does not reduce the risk of recurrent stroke.
Previous studies have shown an association between raised levels of total homocysteine and the risk of stroke and heart disease (Stroke 2004;35:169-74). Folic acid, pyridoxine (vitamin B-6), and cobalamin (vitamin B-12) are known to reduce plasma homocysteine levels, but the effectiveness of homocysteine lowering therapy to reduce the risk of stroke has not been confirmed by randomised trials.
Dr James Toole of Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues conducted a double blind, randomised controlled trial from September 1996 to May 2003 to determine whether high doses of folic acid, vitamin B-6, and vitamin B-12 reduce the risk of an additional stroke over a two year period, compared with low doses of these vitamins (JAMA 2004;291:621-622).
The study comprised 3680 adults who had had a non-disabling stroke; they were enrolled at 56 sites in the United States, Canada, and Scotland. Patients were randomly assigned to receive once daily doses of either a high dose formulation (containing 25 mg vitamin B-6, 0.4 mg vitamin B-12, and 2.5 mg folic acid) or a low dose formulation (containing 200 micrograms vitamin B6, 6 micrograms vitamin B-12, and 20 micrograms folic acid); 1827 patients were assigned to the high dose group, 1853 to the low dose group.
Mean reduction of total homocysteine was greater in the high dose group than in the low dose group but no significant treatment effect on any end point. The chance of an event, including stroke and death, within two years was 18% in the high dose group and 18.6% in the low dose group. The risk of ischaemic stroke within two years was 9.2% for the high dose and 8.8% for the low dose groups.
However, the authors noted a "persistent and graded association between baseline total homocysteine level and outcomes."
A total homocysteine level of 3 micromol/litre lower was associated with a 10% lower risk of stroke, a 26% lower risk of coronary heart disease events, and a 16% lower risk of death in the low dose group; the reduced risks for the high dose group were non-significant (2%, 7%, and 7% lower respectively).
Dr Toole said the "effect of lowering homocysteine levels might have been blunted by the fact that the people in the study were already getting diets fortified with folic acid," after the initiation of a US government policy in 1998 to fortify grain foods with folic acid. Dr Toole postulated that patients already receiving folic acid supplementation might not have experienced an additional reduction in their homocysteine level that was of a sufficient magnitude to show a significant benefit.(New York Scott Gottlieb)
Previous studies have shown an association between raised levels of total homocysteine and the risk of stroke and heart disease (Stroke 2004;35:169-74). Folic acid, pyridoxine (vitamin B-6), and cobalamin (vitamin B-12) are known to reduce plasma homocysteine levels, but the effectiveness of homocysteine lowering therapy to reduce the risk of stroke has not been confirmed by randomised trials.
Dr James Toole of Wake Forest University School of Medicine, Winston-Salem, North Carolina, and colleagues conducted a double blind, randomised controlled trial from September 1996 to May 2003 to determine whether high doses of folic acid, vitamin B-6, and vitamin B-12 reduce the risk of an additional stroke over a two year period, compared with low doses of these vitamins (JAMA 2004;291:621-622).
The study comprised 3680 adults who had had a non-disabling stroke; they were enrolled at 56 sites in the United States, Canada, and Scotland. Patients were randomly assigned to receive once daily doses of either a high dose formulation (containing 25 mg vitamin B-6, 0.4 mg vitamin B-12, and 2.5 mg folic acid) or a low dose formulation (containing 200 micrograms vitamin B6, 6 micrograms vitamin B-12, and 20 micrograms folic acid); 1827 patients were assigned to the high dose group, 1853 to the low dose group.
Mean reduction of total homocysteine was greater in the high dose group than in the low dose group but no significant treatment effect on any end point. The chance of an event, including stroke and death, within two years was 18% in the high dose group and 18.6% in the low dose group. The risk of ischaemic stroke within two years was 9.2% for the high dose and 8.8% for the low dose groups.
However, the authors noted a "persistent and graded association between baseline total homocysteine level and outcomes."
A total homocysteine level of 3 micromol/litre lower was associated with a 10% lower risk of stroke, a 26% lower risk of coronary heart disease events, and a 16% lower risk of death in the low dose group; the reduced risks for the high dose group were non-significant (2%, 7%, and 7% lower respectively).
Dr Toole said the "effect of lowering homocysteine levels might have been blunted by the fact that the people in the study were already getting diets fortified with folic acid," after the initiation of a US government policy in 1998 to fortify grain foods with folic acid. Dr Toole postulated that patients already receiving folic acid supplementation might not have experienced an additional reduction in their homocysteine level that was of a sufficient magnitude to show a significant benefit.(New York Scott Gottlieb)