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Lancet. 2000 Feb 12;355(9203):517-22.

Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.

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Department of General Surgery, University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands.



A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease.


We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography.


Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively).


Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

[Indexed for MEDLINE]

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